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Hypoglycemic effect of inulin combined with ganoderma lucidum polysaccharides in T2DM rats
Abstract
It has been reported that both inulin and ganoderma lucidum polysaccharides are conducive to glucose metabolism. The aim of present study was to explore the hypoglycemia effect and molecular mechanism of the inulin combined with ganoderma lucidum polysaccharides in type 2 diabetic mellitus (T2DM) rats. T2DM rats were induced by high fat diet (HFD) and streptozotocin (STZ). Then the inulin and ganoderma lucidum polysaccharides were administered orally to the T2DM rats for 5 weeks. Subsequently, the glycometabolism relevant parameters were evaluated in all rats, and the molecular mechanism including the key mRNA levels and protein expressions in PI3K/Akt pathway was explored. The results showed that the combination of inulin and ganoderma lucidum polysaccharides could significantly improve the glucose and lipid metabolism related parameters in T2DM rats, which seemed to be related to enhancing the insulin sensitivity, increasing the glycogen synthesis and facilitating the glucose transportation by regulating the PI3K/Akt pathway.
... Diabetes mellitus is a metabolic disease characterized by hyperglycemia induced by insulin resistance, of which T2DM accounts for 90-95% [1]. Type 2 diabetes mellitus (T2DM) is mainly manifested as hyperglycemia, abnormal lipid metabolism, oxidative stress, and tissue damage [2], leading to micro-and macro-vascular complications, vision loss, cardiac failure, and other complications [3]. ...
... In this study, consistent with the findings of Liu et al. [1], T2DM rats induced by HFD/STZ developed insulin resistance, likely related to the overexpression of inflammatory factor TNF-α [55], which required more insulin secretion, leading to insulin accumulation. After 7 weeks of F-OPPF intervention, the changes in pancreatic indices (FINS, ISI, and HOMA-IR) compared to the DC group indicated that F-OPPF improved insulin resistance and increased insulin sensitivity in T2DM rats without significantly promoting insulin secretion by islet cells. ...
... Current in vivo research on the improvement of glucose metabolism by GL mainly focuses on polysaccharides. Similar to the findings of this study, Liu et al. [1] reported that GL polysaccharides improved the glucose metabolism-related parameters in T2DM rats by enhancing insulin sensitivity, increasing glycogen synthesis, and facilitating glucose transportation. The enhanced hypoglycemic effect post-fermentation may stem from the enhanced α-amylase and αglucosidase inhibitions, which can be attributed to bioactive compounds secreted by GL mycelium, including GL triterpenes, polysaccharides, and phenol compounds, along with the release of bioactive components in the substrate. ...
Dietary intervention is the basis for the treatment of diabetes mellitus. This study employed Ganoderma lucidum (GL) mycelium to ferment a compound medium of oat and purple potato (OPP), optimized fermentation conditions to increase the triterpene content in the resulting product (F-OPPF), and systematically investigated the impact of fermentation on the nutritional quality, structural characteristics, and functional properties of OPP. The results indicated that the triterpene content in F-OPPF significantly increased from 8.53 mg/g to 17.23 mg/g under optimal conditions (temperature: 28 °C, inoculum size: 10%, material quantity: 36 g/250 mL, and fermentation time: day 13). Fermentation resulted in enhanced nutritional quality, with increased contents of protein, soluble protein, crude fiber, ash, mineral elements, essential amino acids, polysaccharides, flavonoids, and total phenols. Mycelium not only enveloped the OPP surface but also penetrated its interior, forming a porous honeycomb-like structure. The types of reactive groups and crystals (C + V-type) were not changed after fermentation, while the crystallinity increased. F-OPPF exhibited positive changes in thermogravimetric properties, antioxidant and hypoglycemic activities, and adsorption capacity of insoluble dietary fiber. Additionally, incorporating F-OPPF into the diet markedly reduced fasting blood glucose levels and promoted weight gain in T2DM rats induced by a high-fat diet and streptozotocin. The fermented groups exhibited improvements in glyco- and lipo-metabolism, oxidative stress, and the function and pathological morphology of the pancreas, liver, and kidneys compared to the unfermented group. Collectively, these findings suggested that GL mycelium fermentation enhanced the nutritional and functional values of OPP, and F-OPPF holds potential as a raw material for developing diabetic-friendly foods.
... Very little is known about the additive effects of G. lucidum polysaccharides. Liu et al. [85] conducted research on rats with HFD/STZ-induced type 2 diabetes. A mixture of inulin and polysaccharides extracted from G. lucidum, when taken orally, dramatically improved body weight and balanced food consumption by enhancing carbohydrate utilization. ...
... Glycogen levels in the liver and skeletal muscle are a useful indirect measure of insulin action; therefore, this is noteworthy. The data obtained indicate that the synergistic effect of inulin and G. lucidum polysaccharides may increase gluconeogenesis and hence control glucose levels [85]. ...
... In addition, it may influence glycogen production by inhibiting the phosphorylation of glycogen synthase kinase 3β (GSK3). The combination of G. lucidum polysaccharides and inulin improved insulin sensitivity in diabetic rats, as shown by an up-regulation of PI3K/Akt pathway gene expression and protein synthesis and an increase in Akt phosphorylation compared to the inulin group [85]. ...
in (Y.K.M.) † These authors contributed equally to this work. Abstract: Diabetes mellitus is a complex illness in which the body does not create enough insulin to control blood glucose levels. Worldwide, this disease is life-threatening and requires low-cost, side-effect-free medicine. Due to adverse effects, many synthetic hypoglycemic medications for diabetes fail. Mushrooms are known to contain natural bioactive components that may be anti-diabetic; thus, scientists are now targeting them. Mushroom extracts, which improve immune function and fight cancer, are becoming more popular. Mushroom-derived functional foods and dietary supplements can delay the onset of potentially fatal diseases and help treat pre-existing conditions, which leads to the successful prevention and treatment of type 2 diabetes, which is restricted to the breakdown of complex polysaccharides by pancreatic-amylase and the suppression of intestinal-glucosidase. Many mushroom species are particularly helpful in lowering blood glucose levels and alleviating diabetes symptoms. Hypoglycaemic effects have been observed in investigations on Agaricussu bru-fescens, Agaricus bisporus, Cordyceps sinensis, Inonotus obliqus, Coprinus comatus, Ganoderma lucidum, Phellinus linteus, Pleurotus spp., Poria cocos, and Sparassis crispa. For diabetics, edible mushrooms are high in protein, vitamins, and minerals and low in fat and cholesterol. The study found that bioac-tive metabolites isolated from mushrooms, such as polysaccharides, proteins, dietary fibers, and many pharmacologically active compounds, as well as solvent extracts of mushrooms with unknown metabolites, have anti-diabetic potential in vivo and in vitro, though few are in clinical trials.
... Some SDFs act by improving insulin release, sensitivity, and pancreatic β-cell performance. Also, there are new insights on their positive effects on GLP-1 and enzymes related to glycolysis and gluconeogenesis like protein kinase C, glycogen synthase kinase-3 (GSK-3), hexokinase, glycogen synthase, glycogen phosphorylase, hepatic glucose-6-phosphatase, fructose-1,6-bisphosphatase, and phosphorylase (Liu et al., 2019). All antidiabetic mechanisms are illustrated in Figure 2 (Kasabri et al., 2011). ...
... Ganoderma lucidum polysaccharides synergistically exerted antidiabetic properties in the HFD/STZinduced diabetic Sprague Dawley rats administered for 5 weeks(Liu et al., 2019). This combination effectively modulated the PI3K/Akt signaling transduction pathway which controls the metabolic pathway of glucose and insulin. ...
Diabetes mellitus is a globally metabolic endocrine syndrome marked by a deficiency of insulin secretion (type-1 DM) or glucose intolerance arising from insulin response impairment (type-2 DM) leading to abnormal glucose metabolism. With an increasing interest in natural dietary components for diabetes management, the identification of novel agents witnessed major discoveries. Plant-derived mucilage, pectin, and inulin are important non-starch polysaccharides that exhibit effective antidiabetic properties often termed soluble dietary fiber (SDF). SDF affects sugar metabolism through multiple mechanisms affecting glucose absorption and diffusion, modulation of carbohydrate metabolizing enzymes (α-amylase and α-glucosidase), ameliorating β-pancreatic cell dysfunction, and improving insulin release or sensitivity. Certain SDFs inhibit dipeptidyl peptidase-4 and influence the expression levels of genes related to glucose metabolism. This review is designed to discuss holistically and critically the antidiabetic effects of major SDF and their underlying mechanisms of action. This review should aid drug discovery approaches in developing novel natural antidiabetic drugs from SDF. K E Y W O R D S diabetes mellitus, dipeptidyl peptidase-4, insulin resistance, mucilage, pectin, α-amylase
... GLP также оказывали гипогликемическое действие на моделях мышей с диабетом (T2DM), у которых улучшались уровни глюкозы и метаболизм липидов [35], [36]. ...
... Ганодеран, выделенный из клеточной стенки Ganoderma lingzhi/G. sichuanense показал самую высокую противоопухолевую активность (уровень ингибирования 94%) у мышей с саркомой и 37% антикомплементарную активность [35]. ...
... SD rats (male, 180-200 g) were fed with a high-fat diet for 4 weeks. Afterwards, the rats received an intraperitoneal streptozotocin (STZ) injection at a dose of 30 mg/kg in cold citrate buffer (pH 4.5) to induce T2DM [40]. After 72 h, rats with fasting glucose levels above 16.7 mmol/L were considered to be T2DM rats and used in following experiments [40]. ...
... Afterwards, the rats received an intraperitoneal streptozotocin (STZ) injection at a dose of 30 mg/kg in cold citrate buffer (pH 4.5) to induce T2DM [40]. After 72 h, rats with fasting glucose levels above 16.7 mmol/L were considered to be T2DM rats and used in following experiments [40]. ...
Diabetes has been associated with postoperative complications, such as increased risk of tissue infection and impaired tissue repair caused by destabilization of hypoxia-inducible factor-1α (HIF-1α). Consequently, it is imperative to fabricate anti-bacterial and pro-regenerative small-diameter vascular grafts for treating cardiovascular disease in diabetic patients. Herein, we developed electrospun cobalt ion (Co²⁺)-loaded poly (ε-caprolactone) (PCL) microfiber vascular grafts (PCL-Co grafts). The released Co²⁺ significantly increased the stabilization of HIF-1α in high-glucose (HG)-treated HUVECs (HG-HUVECs) and macrophages (HG-macrophages). This resulted in enhanced cell migration, nitric oxide production, and secretion of bioactive factors by HG-HUVECs, and polarization of HG-macrophages toward M2 phenotypes in vitro. The Co²⁺ also conferred anti-bacterial properties to the grafts, while not perturbing the inherent anti-bacterial activities of HG-macrophages. Following abdominal artery implantation into type 2 diabetes mellitus (T2DM) rats, PCL-Co grafts were evaluated for performance in infection (grafts pre-contaminated with Staphylococcus aureus) and prophylaxes models (grafts alone). PCL-Co grafts prevented the incidence of subsequent infection in prophylaxes model and effectively inhibited the bacterial growth in the infection model. PCL-Co grafts also significantly enhanced cellularization, vascularization, endothelialization, contractile SMC regeneration and macrophages polarization in both models. Collectively, PCL-Co grafts exhibited the potential to combat infection and improve tissue regeneration under diabetes conditions.
... These findings demonstrate that polysaccharides not only enhance innate and adaptive immunity but also improve vaccine-induced antigen-specific immune responses as adjuvants. Recent studies, including our own, have reported various biological activities of polysaccharides isolated from natural products, such as antitumor [12,13], antioxidant [14,15], and hypoglycemic activities [16,17]. The biological activities of polysaccharides are related to their physicochemical characteristics [18], bioavailability [19], and conjugation sites [20]. ...
To investigate the structure–antioxidant activity relationship, Pleurotus ferulae polysaccharides were extracted using ultrasonic (U-PFPS) and microwave/ultrasonic-assisted methods (MU-PFPS). Compared to U-PFPS with a molecular weight of 1.566 × 103 kDa, MU-PFPS exhibited a lower molecular weight of 89.26 kDa. In addition, unlike U-PFPS, which is primarily composed of glucose (Glu:Man:Gal = 91.1:3.5:5.4), MU-PFPS has a more balanced composition of Glu:Man:Gal in the ratio of 39.4:27.8:32.8 and contains more branched chains. Furthermore, antioxidant analysis revealed that high concentration (at concentrations above 600 μg/mL) MU-PFPS demonstrated stronger protective effects against oxidative damage in RAW264.7 cells than U-PFPS did. Collectively, these data suggest that lower molecular weight and higher branching degree of polysaccharides at appropriate concentrations may correlate with enhanced antioxidant enzyme activities. Our work provides a method for isolating polysaccharides with higher antioxidant activity and offers insights into the structure–activity relationship of polysaccharides, laying the foundation for future applications in polysaccharide modification and structural characterization.
... It is obvious that PI3K/Akt signaling pathway plays a notable role in regulating blood glucose levels and insulin signal transduction [57][58][59] . Increasing investigations have demonstrated that EFP can regulate PI3K/Akt signaling pathway, regulate blood glucose level, and increase insulin levels. ...
Diabetes mellitus (DM) is a chronic metabolic disorder with the feature of hyperglycemia, which has severely endangered human health. Edible fungus polysaccharides (EFP), which has great development potential, have attracted enormous attention since their natural and safe characteristics as well as obvious benefits against diabetes. This review summarized the hypoglycemic effect of EFP and the underlying mechanism against diabetes by inhibiting digestive enzyme activity, increasing insulin sensitivity and resistance, improving pancreatic function and lipid metabolism, alleviating oxidative stress and inflammation, regulating gut microbiota and signal transduction. In addition, the relationships between structure and hypoglycemic activity as well as future prospect of EFP were also discussed. This current review provides valuable insights for readers and healthcare professionals developing preventive and therapeutic of diabetes and development of functional products or foods of edible fungi in the future.
... Research conducted by Nishimura et al. (2018) showed that chicory root extract containing inulin for four weeks in adults can reduce hemoglobin A1c (HbA1c) levels [7]. Another study in 2019 revealed that type 2 diabetes mellitus (T2DM) rats induced by a high-fat diet (HFD) and streptozotocin (STZ) for five weeks displayed significantly enhanced insulin sensitivity, increased glycogen synthesis, and improved glucose transport activation through the PI3K/Akt pathway [8]. Findings from research involving diabetic rats receiving Lactobacillus plantarum 1058 (ATCC 8014) and inulin supplements for eight weeks indicated reduced hyperglycemia, insulin resistance, hyperlipidemia, oxidative stress, and increased insulin and leptin levels in the hypothalamus of the rats [9]. ...
Background
Dahlia (Dahlia variabilis), a widely cultivated ornamental plant in Indonesia, is known to contain 84.08% inulin in its tubers. Numerous studies have demonstrated the antidiabetic potential of inulin from various plant sources. However, most of the research is in the form of a mixture of inulin with other active substances, and no one has analyzed the effects of inulin derived from dahlia tubers. This study examines the effect of inulin from dahlia tuber extract on blood glucose levels, serum insulin expression, pancreatic tissue insulin expression, homeostatic model assessment of insulin resistance (HOMA-IR), and the extent of insulitis in diabetic rats.
Methods
In this experimental study, 20 male Wistar rats were randomly allocated to five groups. Group I served as the control, Group II as the STZ-induced diabetic group, Group III as the STZ-induced diabetic group treated with inulin (0.5 g/kgBW), Group IV as the STZ induced diabetic group treated with inulin (1.0 g/kgBW), and Group V as the STZ-induced diabetic group treated with inulin (1.5 g/kgBW). The inulin was administered for 21 days. The degree of insulitis was evaluated using a scoring system, serum insulin concentration via ELISA, and insulin expression in the pancreas through immunohistochemistry.
Results
Administration of inulin from dahlia tubers significantly reduced serum glucose concentrations in diabetic rats. Notably, only inulin extracts at doses of 1 g/kgBW and 1.5 g/kgBW showed a significant reduction in insulitis and HOMA-IR index in diabetic rats, while the 0.5 g/kgBW inulin extract reduced insulitis without affecting HOMA-IR. Inulin extract administration did not affect insulin expression in serum or pancreatic tissue.
Conclusions
Inulin from dahlia tuber can exert antidiabetic properties by improving insulin resistance and insulitis. These studies suggest the great potential of dahlia tubers as the source of inulin for prebiotic functional foods.
... Although these did not reach the levels observed for the healthy mice (DC group), the effect was similar to that of metformin (p > 0.05). Thus, P. alkekengi polysaccharides displayed the ability to alleviate insulin resistance in the T2DM mice, which is consistent with the results previously observed for polysaccharides extracted from inulin, Ganoderma lucidum, and tea [52,53]. Consequently, P. alkekengi polysaccharide extract may reduce the risk of diseases related to insulin resistance and exert a positive effect on blood glucose regulation. ...
Type 2 diabetes mellitus (T2DM) is a common metabolic disease that adversely impacts patient health. In this study, a T2DM model was established in ICR mice through the administration of a high-sugar and high-fat diet combined with the intraperitoneal injection of streptozotocin to explore the hypoglycemic effect of polysaccharides from Physalis alkekengi L. After six weeks of treatment, the mice in the high-dosage group (800 mg/kg bw) displayed significant improvements in terms of fasting blood glucose concentration, glucose tolerance, serum insulin level, insulin resistance, and weight loss (p < 0.05). The polysaccharides also significantly regulated blood lipid levels by reducing the serum contents of total triglycerides, total cholesterol, and low-density lipoproteins and increasing the serum content of high-density lipoproteins (p < 0.05). Furthermore, they significantly enhanced the hepatic and pancreatic antioxidant capacities, as determined by measuring the catalase and superoxide dismutase activities and the total antioxidant capacity (p < 0.05). The results of immunohistochemistry showed that the P. alkekengi polysaccharides can increase the expression of GPR43 in mice colon epithelial cells, thereby promoting the secretion of glucagon-like peptide-1. In summary, P. alkekengi polysaccharides can help to regulate blood glucose levels in T2DM mice and alleviate the decline in the antioxidant capacities of the liver and pancreas, thus protecting these organs from damage.
... It has been reported that supplementation of L. plantarum and inulin could improve the gut microbial composition as well as reduce the levels of inflammatory cytokines in T2DM rats [19]. In addition, INU can ameliorate metabolic disorders in high-fat diet rats [20] and may increase glycogen synthesis and facilitate glucose transportation by regulating the PI3K/Akt pathway in T2DM rats [21]. However, the effect of L. plantarum and L. fermentum coordinating with INU on T2DM has not been reported. ...
... Ganoderma lucidum polysaccharides synergistically exerted antidiabetic properties in the HFD/STZinduced diabetic Sprague Dawley rats administered for 5 weeks(Liu et al., 2019). This combination effectively modulated the PI3K/Akt signaling transduction pathway which controls the metabolic pathway of glucose and insulin. ...
Diabetes mellitus is a globally metabolic endocrine syndrome marked by a deficiency of insulin secretion (type-1 DM) or glucose intolerance arising from insulin response impairment (type-2 DM) leading to abnormal glucose metabolism. With an increasing interest in natural dietary components for diabetes management, the identification of novel agents witnessed major discoveries. Plant-derived mucilage, pectin, and inulin are important non-starch polysaccharides that exhibit effective antidiabetic properties often termed soluble dietary fiber (SDF). SDF affects sugar metabolism through multiple mechanisms affecting glucose absorption and diffusion, modulation of carbohydrate metabolizing enzymes (α-amylase and α-glucosidase), ameliorating β-pancreatic cell dysfunction, and improving insulin release or sensitivity. Certain SDFs inhibit dipeptidyl peptidase-4 and influence the expression levels of genes related to glucose metabolism. This review is designed to discuss holistically and critically the antidiabetic effects of major SDF and their underlying mechanisms of action. This review should aid drug discovery approaches in developing novel natural antidiabetic drugs from SDF.
... Compound formulations, which consist of two or more ingredients, have the potential to offer multiple targeting effects with a low incidence of side effects [40]. For instance, Ganoderma lucidum mycelium has been found to regulate the intestinal flora, enhance intestinal barrier function, and modulate both intestinal immune function and microbial abundance in rats [41]. ...
Abstracts
The bioactivities of Ganoderma lucidum, Grifola frondosa, and American ginseng have been extensively studied and documented. However, the effects of their complexes on the structural properties of intestinal microbiota and fecal metabolism remain unclear. Therefore, this paper aims to present a preliminary study to shed light on this aspect. In this study, an immunocompromised mouse model was induced using cyclophosphamide, and Ganoderma lucidum, Grifola frondosa, and American ginseng extract formulation (referred to as JGGA) were administered via gavage to investigate their modulatory effects on gut microbiota and fecal metabolism in mice. The effects of JGGA on immune enhancement were explored using serum test kits, hematoxylin–eosin staining, 16SrDNA high-throughput sequencing, and UHPLC-QE-MS metabolomics. The findings revealed potential mechanisms underlying the immune-enhancing effects of JGGA. Specifically, JGGA administration resulted in an improved body weight, thymic index, splenic index, carbon scavenging ability, hypersensitivity, and cellular inflammatory factor expression levels in mice. Further analysis demonstrated that JGGA reduced the abundance of Firmicutes, Proteobacteria, and Actinobacteria, while increasing the abundance of Bacteroidetes. Additionally, JGGA modulated the levels of 30 fecal metabolites. These results suggest that the immune enhancement observed with JGGA may be attributed to the targeted modulation of gut microbiota and fecal metabolism, thus promoting increased immunity in the body.
... In this study, there were significant differences in GSH-PX and SOD activities and serum MDA between the MG group and treatment groups. Furthermore, increased doses of TMSP-1 pushed the activities of GSH-PX and SOD and MDA content closer to the respective values for the NG group, which was similar to the result of Liu et al. [57]. At the same time, patients with diabetes are often accompanied by dyslipidemia, such as elevated cholesterol and triglyceride levels. ...
In this manuscript, polysaccharide (TMSP) was isolated from Trichosanthes kirilowii Maxim. seed shell. The homogeneous polysaccharide (TMSP-1; molecular weight: 690.239 kDa) was purified by column chromatography (DEAE-cellulose-52 and Sephadex G-150). The result of monosaccharide composition showed that TMSP-1 consisted of D-mannose, D-glucose, D-galactose, and glucuronic acid in a molar ratio of 2.01 : 1.98 : 1.87 : 1. Methylation analysis showed that TMSP-1 was made up of →3)-D-Galp-(1→, D-Glcp-(1→, →4)-D-Manp-(1→, →6)-D-Galp-(1→, →4)-D-Galp-(1→, and →4,6)-D-Manp-(1→. The microscopic conformation of TMSP-1 showed a regular flake-like structure that was inlaid with small holes. The α-glucosidase inhibitory rate of TMSP-1 reached 52.23% when the concentration of TMSP-1 was 8 mg/mL, which confirmed the potential hypoglycemic activity of TMSP-1 in vitro. In vivo results showed that type 2 diabetes causes a significant increase in organ index and TMSP-1 recovered the organ index in mice ( P < 0.05 ). Furthermore, TMSP-1 reversed the increase of liver and kidney weight and the indicators of abnormality. This research lays a foundation for research on the polysaccharides of Trichosanthes kirilowii Maxim. seed shell in hypoglycemia.
... 49 Liu et al. found that Ganoderma lucidum polysaccharides significantly upregulated the mRNA and protein levels of GLUT4 and GS, and reduced the GSK-3β expression in the liver and skeletal muscle, thereby promoting glucose uptake and glycogen synthesis. 50 It is reported that increased glucagon production decreases Akt activity and enhances FoxO1-mediated hepatic gluconeogenesis. 51 Similar investigation also found that knockout of the glucagon receptor (GCGR) obviously alleviated metabolic syndrome in diabetic mice. ...
Unhealthy dietary pattern-induced type 2 diabetes mellitus poses a great threat to human health all over the world. Accumulating evidence has revealed that the pathophysiology of type 2 diabetes mellitus is closely associated with the dysregulation of glucose metabolism and energy metabolism, serious oxidative stress, prolonged endoplasmic reticulum stress, metabolic inflammation and intestinal microbial dysbiosis. Most important of all, insulin resistance and insulin deficiency are two key factors inducing type 2 diabetes mellitus. Nowadays, natural polysaccharides have gained increasing attention owing to their numerous health-promoting functions, such as hypoglycemic, energy-regulating, antioxidant, anti-inflammatory and prebiotic activities. Therefore, natural polysaccharides have been used to alleviate diet-induced type 2 diabetes mellitus. Specifically, this review comprehensively summarizes the underlying hypoglycemic mechanisms of natural polysaccharides and provides a theoretical basis for the development of functional foods. For the first time, this review elucidates hypoglycemic mechanisms of natural polysaccharides from the perspectives of their regulatory effects on glucose metabolism, insulin resistance and mitochondrial dysfunction.
... The combination of inulin and Ganoderma lucidum polysaccharides promotes the synthesis of glycogen, a polysaccharide that serves as the main form of glucose storage [136]. The polysaccharides of the brown algae Undaria pinnatifida can protect pancreatic islet cells from damage while stimulating glycogen synthesis in the liver [137]. ...
The prevalence of diabetes mellitus is one of the major medical problems that the modern world is currently facing. Type 1 and Type 2 diabetes mellitus both result in early disability and death, as well as serious social and financial problems. In some cases, synthetic drugs can be quite effective in the treatment of diabetes, though they have side effects. Plant-derived pharmacological substances are of particular interest. This review aims to study the antidiabetic properties of secondary plant metabolites. Existing review and research articles on the investigation of the antidiabetic properties of secondary plant metabolites, the methods of their isolation, and their use in diabetes mellitus, as well as separate articles that confirm the relevance of the topic and expand the understanding of the properties and mechanisms of action of plant metabolites, were analyzed for this review. The structure and properties of plants used for the treatment of diabetes mellitus, including plant antioxidants, polysaccharides, alkaloids, and insulin-like plant substances, as well as their antidiabetic properties and mechanisms for lowering blood sugar, are presented. The main advantages and disadvantages of using phytocomponents to treat diabetes are outlined. The types of complications of diabetes mellitus and the effects of medicinal plants and their phytocomponents on them are described. The effects of phytopreparations used to treat diabetes mellitus on the human gut microbiota are discussed. Plants with a general tonic effect, plants containing insulin-like substances, plants-purifiers, and plants rich in vitamins, organic acids, etc. have been shown to play an important role in the treatment of type 2 diabetes mellitus and the prevention of its complications.
... Diabetes causes the pancreatic islets to lose their normal function of regulating blood glucose, resulting in abnormal blood glucose concentrations in organisms [47]. Table 4 showed that, with the exception of the CON group, all five groups were hyperglycemic, indicating that STZ modeling was successful. ...
Armillaria mellea polysaccharides (AMPs) were obtained by ultrasonic assisted extraction (U), enzyme assisted extraction (E) and ultrasonic-enzyme assisted extraction (UE), respectively. The yield of UE-AMPs (6.32 ± 0.14%) was 1.64 times higher than that of U-AMPs (3.86 ± 0.11%) and 1.21 times higher than that of E-AMPs (5.21 ± 0.09%); meanwhile, the highest total sugar content and the lowest protein content were found in UE-AMPs. AMPs obtained from the three extraction methods had the same monosaccharide composition but in different proportions, allowing UE-AMPs to have the most potent antioxidant activity. The antidiabetic activity of UE-AMPs was investigated in streptozotocin (STZ)-induced diabetic mice. UE-AMPs, when given by gavage, greatly prevented weight loss, increased water intake, and considerably decreased blood glucose levels in diabetic mice, which were dose-dependent (P < 0.05). In addition, UE-AMPs also had a positive effect on the reduction of lipid levels in the blood, oxidative damage and liver function impairment. The pathological observation by hematoxylin-eosin staining (HE) revealed that UE-AMPs protected the organs of mice from diabetic complications (liver disease and nephropathy). Hence, our findings demonstrate that UE-AMPs are a suitable choice for improving diabetes and its complications and have great application prospects in the fields of natural medicine and functional food.
... Recent studies have shown that inulin may improve rumen fermentation, microbial balance, and growth performance in beef cattle [7]. Further, it is considered that inulin can act in combination with other additives (such as inactivated Bacillus subtilis, magnesium oxide, and polyphenol-rich pomegranate extracts) and may have additional beneficial effects on the livestock, such as improving immunity [8], regulating sugar and lipid metabolism [9], and reducing endotoxemia [10]. ...
The aim of this study was to investigate the impacts of inulin and Chinese gallotannin on the meat fatty acids and urinary metabolites in sheep. Twenty-four healthy (25.80 ± 3.85 kg) weaned Hu lambs of approximately 4.5 months old were equally divided into four groups: control group (basal diet), treatment group I (basal diet +0.1% inulin), treatment group II (basal diet +0.1% inulin +2% Chinese gallotannin), and treatment group III (basal diet +0.1% inulin +2% Chinese gallotannin +4% PEG). The contents of myristic acid (C14:0) and palmitic acid (C16:0) were found to be lower in treatment group II than in the control group (p < 0.05). Moreover, the palmitoleic acid (C16:1) content in treatment group II was notably higher than that in the control group (p < 0.05), while the elaidic acid (C18:1n9t) content in treatment group II was higher than that in other groups (p < 0.05). Besides, the linoleic acid (C18:2n6c) content was higher in the treatment II and control groups than in the treatment I and III groups. Furthermore, compared with the control group, both 4-pyridoxic acid and creatinine in treatment groups I and II were upregulated (p < 0.05), while other metabolites, such as nicotinuric acid, l-threonine, palmitic acid, and oleic acid, were drastically downregulated (p < 0.05). These differential metabolites were found to be mainly involved in nicotinate and nicotinamide metabolism (ko00760), vitamin B6 metabolism (ko00750), and the fatty acid biosynthesis pathway (ko00061). It is concluded that the combination of inulin and Chinese gallotannin in the diet could improve the energy and lipid metabolism of sheep, which may improve both mutton quality and production performance.
... Se-rich polysaccharides extracted from the fruiting body of C. militaris exhibited stronger antiinflammation and anti-lipidemic properties than the same source of Se-deficient polysaccharides (29). Furthermore, a combination of inulin and G. lucidum polysaccharides displayed better activities in improving insulin sensitivity, increasing glycogen synthesis, and ameliorating lipid metabolism than inulin or G. lucidum polysaccharides alone in T2DM rats, demonstrating synergistic actions of inulin and G. lucidum in anti-diabetes (131). ...
Diabetes mellitus (DM) is a global health threat. Searching for anti-diabetic components from natural resources is of intense interest to scientists. Mushroom polysaccharides have received growing attention in anti-diabetes fields due to their advantages in broad resources, structure diversity, and multiple bioactivities, which are considered an unlimited source of healthy active components potentially applied in functional foods and nutraceuticals. In this review, the current knowledge about the roles of oxidative stress in the pathogenesis of DM, the extraction method of mushroom polysaccharides, and their potential biological mechanisms associated with anti-diabetes, including antioxidant, hypolipidemic, anti-inflammatory, and gut microbiota modulatory actions, were summarized based on a variety of in vitro and in vivo studies, with aiming at better understanding the roles of mushroom polysaccharides in the prevention and management of DM and its complications. Finally, future perspectives including bridging the gap between the intervention of mushroom polysaccharides and the modulation of insulin signaling pathway, revealing structure-bioactivity of mushroom polysaccharides, developing synergistic foods, conducting well-controlled clinical trials that may be very helpful in discovering valuable mushroom polysaccharides and better applications of mushroom polysaccharides in diabetic control were proposed.
... Numerous studies have documented beneficial biological activities of polysaccharides, including hypoglycemic, antioxidant, anticoagulant, antitumor, antimutagenic, anticomplementary, antiviral, and antiinflammatory activities (11)(12)(13)14). A Hericium erinaceus polysaccharide reduced glucose levels in normal and alloxaninduced diabetic mice without adverse effects (15), and the polysaccharide from Ganoderma lucidum and Hohenbuehelia serotina displayed hypoglycemic activity (16,17). In many cases, activities of polysaccharides are related to their structure. ...
A novel polysaccharide, Heimioporus retisporus Polysaccharide (HRP) was extracted from the edible mushroom Heimioporus retisporus. HRP had weight-average molecular weight 1,949 kDa and number-average molecular weight 873 kDa, and its major components were arabinose (0.71%), galactose (12.93%), glucose (49.00%), xylose (8.59%), mannose (17.78%), and glucuronic acid (10.99%). Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy revealed that HRP was composed of 1,3-linked β-D-glucose, 1,6-linked β-D-mannose, 1,6-linked β-D-galactose, 1,4-linked β-D-galactose, 1,4-linked β-D-xylose, and 1,5-linked α-L-arabinose. Thermogravimetric analysis indicated that degradation temperature (T0) of HRP was 200°C. In an STZ-induced diabetic mouse model, oral administration of HRP (40 mg/kg/d) for 28 days significantly reduced blood glucose levels, and reduced heart organ index by decreasing expression of IL-6 and TNF-α. Our findings indicate hypoglycemic effect of HRP, and its potential application as a hypoglycemic agent.
... Los estudios epidemiológicos muestran que los alimentos con alto IG y bajos en fibra están asociados con una mayor incidencia de diabetes tipo 2. Por lo tanto, el consumo de carbohidratos de baja digestibilidad como la inulina podría considerarse beneficioso ya que presenta un efecto hipoglucémico (Liu, et al., 2019). El IG y la CG se correlacionan con la calidad de los carbohidratos ingeridos, fibra dietética total, fibra de cereales y con los riesgos de diabetes tipo 2, enfermedad coronaria, accidente cerebrovascular y mortalidad (Kaczmarczyk, et al., 2012;Hardy, et al., 2020). ...
Recientemente en Argentina han incrementado de manera considerable los casos de diabetes mellitus (tipo 2) en adultos debido al sobrepeso, la obesidad y el sedentarismo. Esto ha generado un mayor interés por los alimentos funcionales que brindan beneficios a la salud debido a su aporte de pre y probióticos, antioxidantes, fibras y grasas saludables, entre otros. En este trabajo se elaboró un bocadito saludable con tubérculos, cereales y semillas que aportan fibras solubles y no solubles, inulina que actúa como antiglucemiante, fenoles que son antioxidantes y una mezcla de fructosa, glucosa y colágeno como ligante de todos los ingredientes. La composición óptima del aglutinante se determinó mediante un diseño experimental de mezcla con restricciones (Design Expert), manteniendo el resto de los componentes constantes. Se restringió el contenido máximo y mínimo de glucosa y fructosa a efectos de obtener la mayor proporción de colágeno manteniendo una masticabilidad aceptable. Se prepararon los bocaditos y se optimizó su formulación mediante análisis de textura. En base a las respuestas obtenidas surgieron tres posibles formulaciones, se elaboraron los bocaditos y se realizó un análisis sensorial. Se detectó uno de mayor aceptabilidad y se procedió a su análisis químico.
... Moreover, it was shown that proteins of ganoderma played an important role in reducing blood sugar by stimulating the immune system via activation of Forkhead box P3 (FOXP3+) regulatory cells, CD-18 production, and down-regulating CD-45 [7]. Furthermore, the triterpenoids of ganoderma including different ganoderic acids could ameliorate diabetes complications through inhibition of sorbitol accumulation and reducing intestinal glucose uptake by inhibiting aldose reductase and α-glucosidase secretion [8,9]. The effectiveness of ganoderma lucidum in controlling blood glucose and diabetes complications may be due to its antioxidation and anti-inflammatory properties. ...
This study aimed to evaluate the effects of gastrointestinal digestion on the physicochemical properties and hypoglycemic activity of extracellular polysaccharides from Morchella esculenta (MEPS). The results showed that the MEPS digestibility was 22.57 % after saliva-gastrointestinal digestion and only partial degradation had occurred. Contrarily, after 48 h of fecal fermentation, its molecular weight and molar ratios of the monosaccharide composition varied significantly due to being utilized by human gut microbiota, and the final fermentation rate was 76.89 %. Furthermore, the MEPS-I, the final product of saliva-gastrointestinal digestion still retained significant hypoglycemic activity, it alleviated insulin resistance and increased the IR cells glucose consumption by activating PI3K/AKT signaling pathway. MEPS-I treatment reduced the proportion of Firmicutes to Bacteroidetes, and the relative abundance of beneficial bacteria that enhanced insulin sensitivity and glucose uptake was promoted. This research can provide a theoretical basis for the further development of Morchella esculenta as a health functional food.
Objectives
Trilobatin, a glycosylated dihydrochalcone, has been reported to have anti-diabetic properties. However, the underlying mechanism remains unexplained.
Methods
In this investigation, the regulation of trilobatin on glucose metabolism of insulin resistance (IR)-HepG2 cells and streptozocin (STZ)-induced mice and its mechanism were evaluated.
Key findings
Different doses of trilobatin (5, 10 and 20 μM) increased glucose consumption, glycogen content, hexokinase (HK), and pyruvate kinase (PK) activity in IR-HepG2 cells. Among them, the HK and PK activity in IR-HepG2 cells treated with 20 μM trilobatin were 1.84 and 2.05 times than those of the IR-group. The overeating, body and tissue weight, insulin levels, liver damage, and lipid accumulation of STZ-induced mice were improved after feeding with different doses of trilobatin (10, 50, and 100 mg/kg/d) for 4 weeks. Compared with STZ-induced mice, fasting blood glucose decreased by 61.11% and fasting insulin (FINS) increased by 48.6% after feeding trilobatin (100 mg/kg/d). Meanwhile, data from quantitative real-time polymerase chain reaction (qRT-PCR) revealed trilobatin ameliorated glycogen synthesis via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) signaling pathway in IR-HepG2 cells and in STZ-induced mice. Furthermore, in vitro and in vivo experiments showed that trilobatin ameliorated oxidative stress by regulating the mRNA expression of nuclear erythroid-2 related factor 2 (Nrf2)/kelch-like ECH associated protein-1 (Keap-1) pathway as well as heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase-1 (NQO-1).
Conclusions
Our research reveals a novel pharmacological activity of trilobatin: regulating glucose metabolism through PI3K/Akt/GSK-3β and Nrf2/Keap-1 signaling pathways, improving insulin resistance and reducing oxidative stress. Trilobatin can be used as a reliable drug resource for the treatment of glucose metabolism disorders.
This study aimed to assess the impact of Lactobacillaceae (L or H represents low or high dose), inulin (I), polydextrose (P) combined with aerobic exercise (A) on the composition of...
This study aimed to evaluate the effects of Limosilactobacillus fermentum and Lactiplantibacillus plantarum isolated from human feces coordinating with inulin on the composition of gut microbiota and metabolic profiles in db/db mice. These supplements were administered to db/db mice for 12 weeks. The results showed that the Lactobacillaceae coordinating with inulin group (LI) exhibited lower fasting blood glucose levels than the model control group (MC). Additionally, LI was found to enhance colon tissue and increase the levels of short-chain fatty acids. 16S rRNA sequencing revealed that the abundance of Corynebacterium and Proteus, which were significantly increased diabetes. in the MC group compared with NC group, were significantly decreased by the treatment of LI that also restored the key genera of the Lachnospiraceae_NK4A136_group, Lachnoclostridium, Ruminococcus_gnavus_group,Desulfovibrio, and Lachnospiraceae_UCG-006. Untargeted metabolomics analysis showed thatlotaustralin, 5-hydroxyindoleacetic acid, and 13(S)-HpODE were increased while L-phenylalanine, and L-tryptophan were decreased in the MC group compared with the NC group. However, the intervention of LI reversed the levels of these metabolites in the intestine. Correlation analysis revealed that Lachnoclostridium and Ruminococcus_gnavus_group were negatively correlated with 5-hydroxyindoleacetic acid and 13 (S)-HpODE, but positively correlated with L-tryptophan. 13(S)-HpODE was involved in the "linoleic acid metabolism". L-tryptophan and 5-hydroxyindoleacetic acid were involved in "tryptophan metabolism" and "serotonergic synapse". These findings suggest that LI may alleviate type 2 diabetes symptoms by modulating the abundance of Ruminococcus_gnavus_group and Lachnoclostridium to regulate the pathways of "linoleic acid metabolism", "serotonergic synapse", and" tryptophan metabolism". Our results provide new insights into prevention and treatment of type 2 diabetes.
Diabetes mellitus (DM) is a group of metabolic diseases characterized by hyperglycemia that can occur in children, adults, elderly people, and pregnant women. Oxidative stress is a significant adverse factor in the pathogenesis of DM, especially type 2 diabetes mellitus (T2DM), and metabolic syndrome. Natural polysaccharides are macromolecular compounds widely distributed in nature. Some polysaccharides derived from edible plants and microorganisms were reported as early as 10 years ago. However, the structural characterization of polysaccharides and their therapeutic mechanisms in diabetes are relatively shallow, limiting the application of polysaccharides. With further research, more natural polysaccharides have been reported to have antioxidant activity and therapeutic effects in diabetes, including plant polysaccharides, microbial polysaccharides, and polysaccharides from marine organisms and animals. Therefore, this paper summarizes the natural polysaccharides that have therapeutic potential for diabetes in the past 5 years, elucidating their pharmacological mechanisms and identified primary structures. It is expected to provide some reference for the application of polysaccharides, and provide a valuable resource for the development of new diabetic drugs.
Polysaccharides LNP-1 and LNP-2 were extracted and purified from Lepista nuda, and their structural characteristics and biological activities were evaluated. The molecular weights of LNP-1 and LNP-2 were determined to be 16,263 Da and 17,730 Da, respectively. The monosaccharide composition analysis showed that LNP-1 and LNP-2 were composed of fucose, mannose, glucose, and galactose in a molar ratio of 1.00:2.42:1.09:4.04 and 1.00:2.39:1.61:4.23, respectively. The structure analysis revealed that these two polysaccharides were mainly composed of T-Fuc, T-Man, T-Glc, 1,6-Glc 1,6-Gal, and 1,2,6-Man, 1,2,6-Gal. Additionally, LNP-2 contained an additional 1,4-Glc glycosidic linkage in comparison to LNP-1. Both LNP-1 and LNP-2 exhibited anti-proliferation effects on A375 cells, but not on HepG2 cells. Furthermore, LNP-2 showed better cellular antioxidant activity (CAA) than LNP-1. RT-PCR results indicated that LNP-1 and LNP-2 could induce macrophages to secrete immune-modulatory factors NO, IL-6, and TNF-α by regulating their mRNA expression. Overall, this study provides a theoretical basis for the further development of the structure-function relationship of polysaccharides from L. nuda.
This study was aimed at investigating the hypoglycemic effect of Chlorella pyrenoidosa functional formulations (CFF), composed of extracts of C. pyrenoudosa, Ganoderma lucidum, and Panax ginseng with chromium-enriched yeast, on streptozotocin (STZ)-induced high-glucose and high-fat diet-fed mice. In this study, CFF significantly reduced the symptoms of weight loss, liver deformation, cecum injury, and jejunal inflammation in type 2 diabetic mice. In addition to enriching gut probiotics, CFF inhibited harmful microorganisms that could affect glycolipid metabolism disorders (GLD) and enhanced production of short-chain fatty acids. In conclusion, CFF may be able to alleviate GLD symptoms. The study suggests that CFF regulates GLD and the possible mechanisms for this regulation. This provides a theoretical basis for developing nutritious and healthy foods.
Inulin, a soluble dietary fiber, is widely found in more than 36 000 plant species as a reserve polysaccharide. The primary sources of inulin, include Jerusalem artichoke, chicory, onion, garlic, barley, and dahlia, among which Jerusalem artichoke tubers and chicory roots are often used as raw materials for inulin production in the food industry. It is universally acknowledged that inulin as a prebiotic has an outstanding effect on the regulation of intestinal microbiota via stimulating the growth of beneficial bacteria. In addition, inulin also exhibits excellent health benefits in regulating lipid metabolism, weight loss, lowering blood sugar, inhibiting the expression of inflammatory factors, reducing the risk of colon cancer, enhancing mineral absorption, improving constipation, and relieving depression. In this review paper, we attempt to present an exhaustive overview of the function and health benefits of inulin.
The main focus of this study was on the protection mechanism of Jerusalem artichoke inulin (DI) against type 2 diabetes mellitus (T2DM) associated with abnormal hepatic lipid metabolism and gut microbiota dysfunction in high-fat diet and streptozotocin-induced diabetic mice. It was determined that the consumption of DI significantly improved the biochemical parameters and physiological indices linked to T2DM, including the reduction in blood glucose, HbA1c, triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels as well as the contents of serum pro-inflammatory cytokines. Supplementation with DI also ameliorated abnormal hepatic lipid metabolism by altering the expression of genes involved in the production and breakdown of lipids and cholesterol. Microbiological analysis showed that DI supplementation resulted in an enrichment of Prevotellaceae UCG-001, Parasutterella, Prevotellaceae UCG-003, and Dubosiella. Metabolomics revealed 89 differential metabolites closely related to DI intervention, and showed that DI supplementation regulated amino acid metabolism (e.g., indole), lipid metabolism (e.g., phosphocholine), cofactor and vitamin metabolism (e.g., cholecalciferol), nucleotide metabolism (e.g., thymine) and the digestive system (e.g., 7-ketolithocholic acid). Overall, Jerusalem artichoke inulin has a remarkable capacity to ameliorate abnormal hepatic lipid metabolism and gut microbiota dysfunction linked to T2DM.
Research progress of active compounds and biological activities of medicinal mushroom-Ganoderma spp., Hericium spp., Phellinus spp., and Cordyceps spp. were summarized systematically. The main active compounds of medicinal mushrooms included are polysaccharides, proteins, triterpenes, meroterpenoids, polyphenols and nitrogen-containing compounds. The biological activities of the compounds cover immunomodulatory activity, antitumor activity, hypoglycemic activity, hepatoprotective activity, and activity of regulation of intellectual flora.
Non-starch polysaccharides (NSPs) have been reported to exert therapeutic potential on managing type 2 diabetes mellitus (T2DM). Various mechanisms have been proposed; however, several studies have not considered the correlations between the anti-T2DM activity of NSPs and their molecular structure. Moreover, the current understanding of the role of NSPs in T2DM treatment is mainly based on in vitro and in vivo data, and more human clinical trials are required to verify the actual efficacy in treating T2DM. The related anti-T2DM mechanisms of NSPs, including regulating insulin action, promoting glucose metabolism and regulating postprandial blood glucose level, anti-inflammatory and regulating gut microbiota (GM), are reviewed. The structure-function relationships are summarized, and the relationships between NSPs structure and anti-T2DM activity from clinical trials are highlighted. The development of anti-T2DM medication or dietary supplements of NSPs could be promoted with an in-depth understanding of the multiple regulatory effects in the treatment/intervention of T2DM.
Black rice and black bean have not yet been fully investigated as healthy foods for their therapeutic effects on type 2 diabetes mellitus (T2DM). In this study, we aimed to evaluate the antidiabetic effects of black rice, black bean husk anthocyanin extracts, and their combination on glycolipid metabolism, gut microbiota, and serum metabolites in T2DM rats. Black bean husk and black rice anthocyanin extracts were administered to T2DM rats by gavage for 4 weeks. The results showed that black rice and black bean husk anthocyanin extracts significantly improved blood glucose, insulin resistance, serum oxidative stress state, lipid metabolism and inflammatory cytokines levels in rats, and alleviated liver damage. Black rice and black bean husk anthocyanin extracts increased the abundance of short-chain fatty acid (SCFA) producing bacteria Akkermansia spp., Phascolarctobacterium spp., Bacteroides spp., and Coprococcus spp., changed the gut microbiota structure; activated AMPK, PI3K, and AKT; inhibited HMGCR, G6pase and PEPCK expression; and inhibited hepatic gluconeogenesis. Moreover, by adjusting the levels of urea, deoxycytidine, L-citrulline, pseudouridine, and other serum metabolites in T2DM rats, the arginine biosynthesis and pyrimidine metabolism pathways were downregulated. The above results indicated that black rice and black bean husk anthocyanin extracts had a significant impact on the development of T2DM.
Inulin is a type of polysaccharide that is commonly found in nature derived from the dahlia tuber plant, and other plants such as chicory, Jerusalem artichoke, Yaco´n potato and asparagus. Inulin is widely used in industry and pharmaceuticals. In the industrial world, inulin is used as a source of natural sweetener, enhances the taste of food, ferments, and is a low-fiber food source. While in the pharmaceutical world, inulin can be used in several studies, one of which is as an anti-diabetic. This study aims to determine the potential of dahlia tuber inulin as an anti-diabetic. The type of research is a narrative review. Search data using three databases, namely Elsevier (SCOPUS), Pubmed and Google Scholar with a limitation of the last 10 years of articles with the keyword "inulin for diabetes", with the PRISMA method. The results showed that inulin works on glucose absorption in the intestine, lowers blood sugar levels, lowers hemoglobin A1c, increases circulating GLP-1, reduces hyperglycemia, reduces insulin resistance (IR) and hyperlipidemia, reduces oxidative stress, increases insulin and leptin levels, facilitates glucose transport of GLUT4 by activating the PI3K/Akt pathway, is anti-inflammatory, and is involved in the expression of several anti-hyperglycemic genes. The conclusion is that dahlia tuber inulin has an anti-diabetic effect.
This study examined the effects of eugenosedin-A (Eu-A) in a streptozotocin (STZ)/nicotinamide-induced rat model of type II diabetes mellitus (T2DM). Six-week-old Sprague-Dawley rats were randomly divided into three groups: (1) RD group, normal rats fed a regular diet (RD), (2) DM group, T2DM rats fed a high-fat diet, and (3) Eu-A group, T2DM rats fed a high fat diet plus oral Eu-A (5 mg/kg/day). After 30 days, the DM group had higher body weight, higher blood glucose and lower insulin levels than the RD group. The DM group also had increased protein expression of glycogen synthase kinase (GSK) in liver and skeletal muscle and decreased protein expression of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), IRS-2, AMP-activated protein kinase (AMPK), glucose transporter-4 (GLUT-4), glucokinase (GCK), and peroxisome proliferator-activated receptor γ (PPAR-γ). STZ/nicotinamide-induced T2DM increased the expression of mitogen-activated protein kinases (MAPKs: p38, ERK, JNK) and inflammatory p65 protein. In the Eu-A treated T2DM rats, however, blood glucose was attenuated and the insulin concentration stimulated. Changes in IR, IRS-1 and IRS-2 proteins as well as AMPK, GLUT-4, GCK, GSK, PPAR-γ, MAPKs, and inflammatory p65 proteins were ameliorated. These results suggested that Eu-A alleviates STZ/nicotinamide-induced hyperglycemia by improving insulin levels and glucose metabolism, and inhibiting the MAPKs- and p65-mediated inflammatory pathway.
Backgrounds and aims:
Type 2 diabetic mellitus (T2DM) as one of the main causes of morbidity and mortality is associated with immune system disturbances and metabolic abnormalities. In the current study we aimed to evaluate the effects of enriched chicory inulin supplementation on liver enzymes, serum calcium and phosphorous concentrations and hematological parameters in patients with T2DM.
Methods:
Forty-six diabetic females patients were randomly allocated into intervention (n=27) and control (n=22) groups. Subjects in the intervention group received a daily dose of 10g of chicory and subjects in control group received a placebo for two months. Anthropometric variables, glucose homeostasis, hematological parameters and metabolic indices including serum alanine aminotransfersae (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), calcium and phosphorous as well as creatinine concentrations, glomerular filtration rate (GFR) and blood pressure were assessed at the beginning and end of the trial.
Results:
Significant reductions in fasting serum glucose (FSG), Hb A1C, AST and ALP concentrations were observed in chicory-treated group. Systolic and diastolic blood pressures were also reduced in chicory-treated group. Serum calcium significantly increased after chicory supplementation but no change in placebo treated group has been occurred (P=0.014). Supplementation with enriched chicory for two months significantly reduced hematocrit and mean corpuscular volume (MCV) values (P<0.05). Changes in serum insulin, creatinine and GFR were not significant.
Conclusion:
The present study showed beneficial effects of oligofructose-enriched chicory on the improvement of the glucose and calcium homeostasis, liver function tests, blood pressure and reduction in hematologic risk factors of diabetes in female patients with T2DM. Further studies in both genders are needed to generalize these findings to total population.
The extract from roasted chicory (Cichorium intybus L.; 菊苣 jú jù) root (chicory root extract), which contains inulin-type fructans, has favorable effects including antihyperglycemic and antidyslipidemic effects and the improvement of bowel movement. In this study, we examined the effects of chicory root extract on blood glucose, lipid metabolism, and fecal properties in 47 healthy adult participants in a randomized, double-blind, placebo-controlled study. The participants were divided into a test group that drank chicory root extract and a placebo group that drank nonchicory root extract (ingesting 300 mL daily for 4 weeks). We performed hematological examinations and body composition measurements, and administered a visual analog scale (VAS) questionnaire for fecal properties at the baseline (Week 0) and after the intervention (Week 4) for the two groups. Although no significant differences in fasting plasma glucose or insulin were observed, hemoglobin A1c was found to decrease by ingesting chicory root extract. No intergroup differences in the levels of lipid metabolism parameters were observed. However, the level of adiponectin was significantly improved in the chicory root extract group when the baseline and postintervention values were compared. In addition, chicory root extract tends to improve the VAS score for fecal properties. These results suggest that chicory root extract could delay or prevent the early onset of diabetes mellitus and improve bowel movements.
The effects of short-chain fructooligosaccharides (scFOS) and xylooligosaccharides (XOS) on growth, feed utilization and liver activity of key enzymes of glycolytic, gluconeogenic, and lipogenic pathways were studied in European sea bass juveniles. This is the first study about the effect of prebiotics on fish glucose metabolism and few and contradictory studies are available about prebiotic effect on lipid metabolism. Fish were fed isoproteic (46%) and isolipidic (15%) diets based on fish meal (FM diets) or plant ingredients (PP diets; 30 FM: 70 PP) as main protein sources. Four other diets were formulated similar to the control diets (PPC; FMC) but including 1% scFOS or 1% XOS (PPFOS, PPXOS, FMFOS and FMXOS diets). Growth performance was higher in fish fed PPXOS diet than PPC diet. No effect of dietary prebiotics on feed efficiency was noticed. Glucokinase activity was higher in fish fed FMFOS and FMXOS diets than FMC diet. Lipogenic enzyme activities (malic enzyme, fatty acid synthetase, glucose-6-phosphate dehydrogenase) were lower in fish fed diets including XOS than in the other groups. Glycolytic (glucokinase, pyruvate kinase) and lipogenic enzyme activities were higher, and gluconeogenic (fructose-1,6-bisphosphatase) enzyme activity was lower in fish fed FM diets than the PP diets. Overall, dietary XOS decreased lipogenesis, independently of dietary protein source, and improved growth performance in fish fed PP diets. In fish fed FM diets, XOS and scFOS increased glycolytic activity. XOS seemed to have good potential to be used as prebiotic in European sea bass.
Acute dehydroepiandrosterone (DHEA) administration improves hyperglycemia in rats with streptozotocin (STZ)-induced type 1 diabetes mellitus. Diosgenin, a steroid structurally similar to DHEA (dehydroepiandrosterone), is contained highly levels in dioscorea; however, it is still unclear whether this natural product improves hyperglycemia in the type 1 diabetes model rats through an increase muscular GLUT4 signaling. After 1 week of STZ injection, fasting glucose level was measured in blood taken from the tail vein every 30min for 150min after injection of diosgenin or dioscorea (3mg/kg). On another day, muscle was resected 150min after diosgenin or dioscorea injections. Serum DHEA level increased significantly 120min after diosgenin or dioscorea injections; concomitantly, blood glucose level decreased significantly. Moreover, GLUT4 translocation, as well as phosphorylation of Akt and PKC ζ/λ, increased significantly by diosgenin or dioscorea administration. However, these effects of diosgenin and dioscorea were blocked by a 5α-reductase inhibitor that inhibits synthesizing dehydrotestosterone (DHT) from testosterone. Additionally, significant correlations were observed between blood glucose level, GLUT4 translocation level, and muscular sex steroid hormone level 150min after the administrations. These results suggest that the diosgenin-induced increase in the DHEA level may contribute to the improvement of hyperglycemia by activating the muscular GLUT4 signaling pathway in type 1 diabetes model rats.
Ganoderma lucidum (M.A. Curtis:Fr.) P. Karst is a popular medicinal mushroom. Scientific reports had shown that the wound healing effects of G. lucidum were partly attributed to its rich polysaccharides. However, little attention has been paid to its potential effects on wounds associated with diabetes mellitus. In this study, we evaluated the wound healing activity of the hot aqueous extract of G. lucidum in streptozotocin-induced diabetic rats. The extract of G. lucidum was standardised based on chemical contents (w/w) of total polysaccharides (25.1%), ganoderic acid A (0.45%), and adenosine (0.069%). Six groups of six rats were experimentally wounded in the posterior neck region. Intrasite gel was used as a positive control and aqueous cream as the placebo. Topical application with 10% (w/w) of mushroom extract-incorporated aqueous cream was more effective than that with Intrasite gel in terms of wound closure. The antioxidant activity in serum of rats treated with aqueous extract of G. lucidum was significantly higher; whereas the oxidative protein products and lipid damage were lower when compared to those of the controls. These findings strongly support the beneficial effects of standardised aqueous extract of G. lucidum in accelerating wound healing in streptozotocin-induced diabetic rats.
The purpose of this study was to evaluate the effects of high performance inulin supplementation on blood glycemic control and antioxidant status in women with type 2 diabetes.
In a randomized, triple-blind controlled trial, 49 females (fiber intake <30 g/day, 25<body mass index <35 kg/m(2)) with type 2 diabetes were recruited from the Iran Diabetes Society and from endocrinology and metabolism clinics associated with the Tabriz University of Medical Science. The participants were divided into one of two groups in which the participants either received 10 g/day of inulin (intervention, n=24) or maltodextrin (control, n=25) for 2 months. Fasting blood samples were obtained and both glycemic control and antioxidant status were determined at baseline and at the end of the study.
At the end of the study period, there were significant decreases in fasting plasma glucose (8.47%), glycosylated hemoglobin (10.43%), and malondialdehyde (37.21%) levels and significant increases in total antioxidant capacity (18.82%) and superoxide dismutase activity (4.36%) in the inulin group when compared to the maltodextrin group (P<0.05). Changes in fasting insulin, homeostasis model assessment of insulin resistance, and catalase activity were not significant in the inulin group when compared with the maltodextrin group. Glutathione peroxidase activity remained unchanged in both groups.
Inulin supplementation may improve some glycemic and antioxidant indices and decrease malondialdehyde levels in women with type 2 diabetes. Further investigations are needed in order to confirm the positive effects that inulin may have on the glycemic and antioxidant indices of patients with type 2 diabetes.
The current study evaluated the glucose-lowering effect of ganoderma lucidum polysaccharides (Gl-PS) in streptozotocin (STZ)-induced diabetic mice. The diabetic mice were randomly divided into four groups (8 mice per group): diabetic control group, low-dose Gl-PS treated group (50 mg/kg, Gl-PS), high-dose Gl-PS treated group (150 mg/kg, Gl-PS) and positive drug control treated group (glibenclamide, 4 mg/kg), with normal mice used as the control group. Body weights, fasting blood glucose (FBG), serum insulin and blood lipid levels of mice were measured. After 28 days of treatment with Gl-PS, body weights and serum insulin levels of the Gl-PS treated groups was significantly higher than that of the diabetic control group, whereas FBG levels was significantly lower. Moreover, total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterol (LDL-C) levels of the Gl-PS treated groups had dropped, whereas the high density lipoprotein cholesterol (HDL-C) levels had increased. In addition, according to acute toxicity studies, Gl-PS did not cause behavioral changes and any death of mice. These data suggest that Gl-PS has an antihyperglycemic effect. Furthermore, considering the Gl-PS effects on lipid profile, it may be a potential hypolipidaemic agent, which will be a great advantage in treating diabetic conditions associated with atherosclerosis or hyperlipidemia.
Aim:
Previous clinical studies have demonstrated that tangganjian (TGJ), a modern Chinese prescribed medicine, has a clinical effect in the treatment of type 2 diabetes mellitus (T2DM) with nonalcoholic fatty liver disease (NAFLD). Our study aimed to investigate whether the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway is involved in this therapeutic effect.
Materials and methods:
T2DM and NAFLD rat models were constructed and treated with three different concentrations of TGJ. Pioglitazone was used as a positive control, along with the model and normal groups. For analyses, blood and livers were collected. Levels of glucose and lipid metabolism indicators, including fasting insulin and total cholesterol, were determined. The expression levels of insulin receptor substrate (IRS), PI3K, and AKT were also determined by western blotting and immunohistochemistry. Liver tissues were stained with hematoxylin & eosin.
Results:
In the high-dose TGJ-treated and positive groups, there was a significant increase in the HDL-C level and decreases in the levels of the fasting blood glucose, 2 h postprandial blood glucose, fasting insulin, triglyceride, total cholesterol, and low-density lipoprotein cholesterol, along with a significant increase in the expression of IRS, PI3K, and AKT in the liver. TGJ could also attenuate or counteract the effects of T2DM and NAFLD in the liver lobules.
Conclusion:
A high concentration of TGJ can improve glucose and lipid metabolism by activating the IRS/PI3K/AKT signaling pathway.
Nonalcoholic fatty liver disease (NAFLD) and type 2 Diabetes Mellitus (T2DM) are highly prevalent diseases and are closely associated, with NAFLD being present in the majority of T2DM patients. In Asian traditional medicine, Mori Cortex is widely used for the treatment of diabetes and hyperlipidemia. However, whether it has a therapeutic effect on T2DM associated with NAFLD is still unknown. The present study showed that the oral treatment with Mori Cortex extract (MCE; 10 g·kg⁻¹·d⁻¹) lowered the blood lipid levels and reversed insulin resistance (IR) in high fat-diet/streptozotocin-induced type 2 diabetes in rats. The expression levels of sterol receptor element-binding protein-1c (SREBP-1c) and carbohydrate-responsive element binding protein (ChREBP), which are involved in steatosis in NAFLD rats, were measured in the liver samples. MCE decreased the protein and mRNA expression levels of SREBP-1c and ChREBP. In conclusion, down-regulation of SREBP-1c and ChREBP might contribute to the protective effect of MCE on hepatic injury and IR in the rats with T2DM associated with NAFLD.
Background:
Aberrations in the activities of key enzymes of carbohydrate metabolism is well documented in diabetes mellitus. Previous studies have shown that active ingredients in the extracts of Berberis aristata exhibits diverse pharmacological activities in animal models.
Objective:
The present study was undertaken to investigate whether berbamine (BBM), an alkaloid from the roots of Berberis aristata can ameliorate the altered activities of carbohydrate metabolic enzymes in high fat diet (HFD)/streptozotocin (STZ) induced diabetic rats.
Results:
Supplementation of HFD for 4 weeks followed by intraperitonial administration of single low dose of STZ (40 mg/kg b.w.) to Sprague Dawley rats resulted in significant hyperglycemia with a decline in plasma insulin levels. The rats also exhibited decreased hemoglobin with an increase in glycated hemoglobin levels. The activities of hexokinase, glucose-6-phosphate dehydrogenase were decreased whereas increases in the activities of glucose-6-phosphatase and fructose-1,6-bisphosphatase were observed in the hepatic tissues of diabetic control rats. Glycogen content in the hepatic and skeletal muscle tissues were found to be decreased in diabetic rats. Oral administration of BBM for 56 days, dose dependently (50, 100, 200 mg/kg b.w.) improved insulin secretion in diabetic treated rats. Immunohistochemical studies on pancreas revealed a strong immunoreactivity to insulin in BBM treated rats. At the effective dose of 100 mg/kg b.w., BBM restored the altered activities of carbohydrate metabolic enzymes and also improved glycogen content in insulin dependent tissues.
Conclusion:
From the biochemical and histochemical data obtained in this study we conclude that BBM ameliorated the activities of metabolic enzymes and maintained glucose homeostasis in HFD/STZ induced diabetic rats and it can be used as a potential phytomedicine for the management of diabetes mellitus.
The consumption of natural and low calorie sugars has increased enormously from the past few decades. To fulfil the demands, the production of healthy sweeteners as an alternative to sucrose has recently received considerable interest. Fructose is the most health beneficial and safest sugar amongst them. It is generally recognised as safe (GRAS) and has become an important food ingredient due its sweetening and various health promising functional properties. Commercially, high fructose syrup is prepared from starch by multienzymatic process. Single-step enzymatic hydrolysis of inulin using inulinase has emerged as an alternate to the conventional approach to reduce complexity, time and cost. The present review, outlines the enzymatic strategies used for the preparation of high fructose syrup from inulin/inulin-rich plant materials in batch and continuous systems, and its conclusions.
Chronic hyperglycemia induces impairment of muscle growth and development in diabetes mellitus (DM). Since skeletal muscle is the major site for disposal of ingested glucose, impaired glucose metabolism causes imbalance between protein synthesis and degradation which adversely affects physical mobility.
In this study, we investigated the effect of tocotrienol rich fraction (TRF) supplementation on skeletal muscle damage in diabetic mice. Diabetes was induced by a high fat diet with streptozotocin (STZ) injection (100 mg/kg) in male C57BL/6 J mice. After diabetes was induced (fasting blood glucose (FBG) levels≥250 mg/dl), normal control (CON) and diabetic control (DMC) groups were administrated with olive oil while, TRF treatment groups were administrated with TRF (dissolved in olive oil) at low dose (100 mg/kg BW, LT) or high dose (300 mg/kg BW, HT) by oral gavage for 12 weeks.
TRF supplementation ameliorated muscle atrophy, plasma insulin concentration, and HOMA-IR in diabetic mice. Moreover, TRF treatment upregulated IRS-1 and Akt levels accompanied by increased translocation of GLUT4. Furthermore, TRF increased mitochondrial biogenesis by activating SIRT1, SIRT3, AMPK, and in diabetic skeletal muscle. These changes were in part mechanistically explained by reduced levels of skeletal muscle proteins related to oxidative stress (4-HNE, protein carbonyls, Nrf2 and HO-1), inflammation (NFkB, MCP-1, IL-6 and TNF-α), and apoptosis (Bax, Bcl₂, and caspase-3) in diabetic mice. Taken together, these results suggest that TRF might be useful as a beneficial nutraceutical to prevent skeletal muscle atrophy associated with diabetes by regulating insulin signaling via AMPK/SIRT1/PGC1α pathways in type 2 diabetic mice.
Protein tyrosine phosphatase 1 B (PTP1B) is one of main causes involved in type 2 diabetes, it dephosphorylates insulin receptor substrate (IRS) and dysregulates insulin signaling pathway, thus inducing insulin resistance. Our previous work first reported that FYGL, a neutral hyperbranched proteoglycan ingredient extracted from Ganoderma lucidum, has hypoglycemic activity in vivo and inhibitory potency on PTP1B in vitro, but the underlying mechanism was still unclear. In this study, we sought to investigate effects of FYGL on insulin signaling pathway involved with PTP1B as the targeting point in hepatocytes. We found that FYGL inhibited overexpression of PTP1B in liver tissues of ob/ob mice and HepG2 cells, significantly improved the phosphorylation of IRS1 on tyrosine residues, activated phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt) cascades and increased phosphorylation of glycogen synthesis kinase-3β (GSK3β), finally enhanced insulin-stimulated glycogen synthesis in HepG2 cells and decreased blood glucose in insulin resistance model mice. Our study clearly illustrated the hypoglycemic mechanism of a novel proteoglycan possibly used in type 2 diabetes management in vivo.
The aim of the study was to evaluate the hypoglycemic effect of low, medium, and high doses of resistant starch type 2(RS2;100, 150, and 200g/kg) for 28days and explore its potential mechanism of this effect in type 2 diabetic rats treated with high-glucose-fat diet and low-dose streptozotocin(STZ). RS2 treatment induced better regulation of lipid in plasma and liver, fructosamine, oral glucose tolerance test, insulin, glucose metabolism and pancreatic damage in diabetic rats. The best hypoglycemic activity was observed after the medium-dose RS2 treatment. Western blot and real-time Polymerase Chain Reaction (RT-PCR)results revealed that phosphoenolpyruvate carboxykinase and glucose-6-phosphatase are involved in glyconeogenesis in the liver, and pancreatic duodenum homeobox 1 controls gluconeogenesis balance by regulating the expression levels of glucose kinase and glucose transport protein 2 in the liver and pancreas. Furthermore, the expression levels of insulin receptor substrate 1 and insulin receptor substrate 2 were enhanced in the pancreas. Results suggested that decreases in the blood glucose levels of diabetic rats fed with RS are regulated through the alteration of the expression levels of the genes related to glucose metabolism and amelioration of pancreatic dysfunction.
Introduction:
Enicostema littorale blume (A. Raynal) is a traditional Indian plant belongs to the Gentianaceae family. A lot of research has been done on this plant for its antidiabetic activity. However, there are no reports on flavonoids from E. littorale for its antidiabetic activity and their mechanism of action. Thus, the aim of this study is to evaluate the antidiabetic activity of Swertisin rich flavonoid fraction (SRF) from Enicostema littorale blume and their mechanism of action.
Materials & methods:
Type 2 Diabetes Mellitus rat model was established by inducing insulin resistance using high fat diet and low dose of streptozotacin injection and was authenticated by HOMA index. The antidiabetic effect of SRF was evaluated on diabetic rats to investigate its long term effects on fasting blood glucose, OGTT, weight of rats, insulin, liver profile, lipid profile, kidney profile, histopathology of liver and pancreas. In addition, antioxidant activity by lipid peroxidation and catalase assay, ex vivo assays and hepatic glycogen content were performed to determine its effect on glycogenesis and hepatic glucose production. Furthermore, the mechanism of action of SRF was evaluated by Real time PCR and the mRNA expression was quantified for Glucokinase (GCK), Insulin receptor substrate (IRS-1), Glucose transporter-2 (GLUT-2) and Glucose transporter-4 (GLUT-4) genes.
Results:
Treatment of diabetic rats with SRF demonstrated significant (p<0.0001) dose dependant hypoglycemic activity as compared to positive control metformin group. A decrease in liver, lipid and kidney function tests was seen as compared to diabetic control indicating normalization of organ function tests. Also, antioxidant activity showed significant decrease in malondialdehyde (MDA) content in liver (p<0.001) as compared to pancreas and increased catalytic activity in liver, kidney, spleen and pancreas. The hepatic glycogen content was significantly (p<0.001) increased in SRF treated rats indicating its inhibition of hepatic glucose production. Furthermore, ex vivo assays showed the significant (p<0.05) increase in glucose uptake by diaphragm. The mRNA expression for GCK, IRS-1, GLUT-2 and GLUT-4 genes showed significant up regulation as compared to diabetic control indicating its mechanism via insulin signalling pathway.
Conclusion:
The studies suggest that SRF ameliorates the insulin resistance by increasing glucose uptake and sensitizing cells towards insulin via IRS1/PI3K/Akt2 pathway.
The leaves of Dacryodes edulis were investigated for their anti-oxidative and anti-diabetic potentials in vitro. Extracts from sequential extraction with solvents of increasing polarity (n-hexane, ethyl acetate, ethanol and aqueous) of the leaves were subjected to in vitro antioxidant assays using the 2,2'-diphenyl-1-picrylhydrazyl (DPPH) scavenging and Ferric reducing antioxidant power (FRAP) protocols respectively. Their inhibitory effects were investigated on α-glucosidase, pancreatic lipases, pancreatic ATPase and glucose-6-phospatase activities. Their antioxidant and anti-apoptotic effects on Fe(2+) - induced oxidative injuries in pancreatic and hepatic tissues were also investigated ex vivo. The ethanol extract was subjected to Gas chromatography mass spectroscopy (GC-MS) and Fourier transform infrared (FTIR) spectroscopic analysis to identify its bioactive chemical constituents. The extracts showed potent free radical scavenging activity and significantly (p<0.05) inhibited all studied enzymes, with the ethanol extract showing greater activities. Superoxide Dismutase (SOD) and Catalase (CAT) activities were significantly (p<0.05) increased in both pancreatic and hepatic tissues with concomitant elevation of reduced glutathione (GSH) levels as well as reduced levels of malondialdehyde (MDA). The extracts significantly inhibited DNA fragmentation. These activities were dose - dependent. Amongst compounds identified, only Kaur-15-ene, Urs-12-ene-3-ol acetate and 2,3,23-trihydroxyolean-12-en-28-oic acid methyl ester showed strong binding affinities when docked with α-glucosidase (PDB ID:3TON). These results indicate the anti-oxidative, anti-diabetic and anti-obesogenic potentials of D. edulis leaves, which gives credence to its antidiabetic folkloric claims.
The present study aimed at exploring the therapeutic potential of standard extract of Bombax ceiba L. leaves (BCE) in type 2 diabetic mellitus (T2DM). Oral administration of BCE at doses of 70, 140, and 280 mg·kg⁻¹, to the normal rats and the high-fat-diet- and streptozotocin-induced T2DM rats were carried out. Effects of BCE on blood glucose, body weight, and a range of serum biochemical parameters were tested, and histopathological observation of pancreatic tissues was also performed. HPLC-ESI-Q/TOF-MS/MS analysis indicated that the chemical composition of BCE mainly contained mangiferin, isoorientin, vitexin, isomangiferin, isovitexin, quercetin hexoside, 2′-trans-O-cumaroyl mangiferin, and nigricanside. BCE caused a significant decrease in the concentrations of fasting blood glucose, glycosylated hemoglobin, total cholesterol, triglyceride, low density lipoprotein-cholesterol, serum insulin, and malondialdehyde, and increases in oral glucose tolerance, high density lipoprotein-cholesterol, and superoxide dismutase in the T2DM model rats. Moreover, considerable pancreatic β-cells protection effect and stimulation of insulin secretion from the remaining pancreatic β-cells could be observed after BCE treatment. The results indicated that BCE exhibited an excellent hypoglycemic activity, and alleviated dyslipidemia which is associated with T2DM. Antioxidant activity and protecting pancreatic β-cells are the possible mechanisms involved in anti-diabetic activity of BCE.
In this work, two carbohydrate polymers, inulin (I) and maltodextrin (MX), were compared as carrying agents in the spray drying of blueberry juice (BJ). The physicochemical properties and the conservation of the antioxidants content were characterized. Both systems, showed non-agglomerated particles and light-purple color appearance. Powders were subjected to the adsorption of water, and the glass transition temperature (Tg) decreased with the water activity. The evolution of the microstructure in the MX-BJ remained unchanged, while the I-BJ presented an abrupt change from amorphous to crystalline. This was corroborated by scanning electron microscopy (SEM), observing in the I-BJ system, the change from spherical into irregular shape particles. In the conservation of the antioxidants content, the MX-BJ showed a better performance. Anyhow, the performance of both carbohydrate polymers as carrying agents in the spray drying of BJ was effective.
Scope:
Chicory inulin is a naturally occurring fructan that is conducive to glucose and lipid metabolism in patients with diabetes mellitus. The present study aims to investigate the mechanism by which chicory inulin improves glucolipid metabolism in diabetic conditions.
Methods and results:
Rats were injected with streptozotocin and fed with high fat diet to induce diabetes, and then administrated with different doses of chicory inulin for 8 weeks. The glycometabolism and lipid metabolism parameters were determined, the activity of insulin receptor substrate (IRS) and mitogen-activated protein kinase (MAPK) pathways were examined by western blot. The effect of chicory inulin on glucose uptake of myoblast and hepatocyte were also measured in vitro. Data were analyzed by student's t test or one-way analysis of variance followed by the Bonferroni post-hoc testing. The results showed that chicory inulin improved glucolipid metabolism, and it activated IRS but suppressed the MAPK pathways in vivo and in vitro.
Conclusion:
Our study demonstrates that chicory inulin, as a nutritional supplement, may be beneficial for the patients with type 2 diabetes mellitus, and the metabolism-modulatory effect seems to be related to the inhibition of JNK and P38 MAPK pathways. This article is protected by copyright. All rights reserved.
Ethnopharmacological relevance:
Ganoderma lucidum (Lin Zhi) has been used to treat diabetes in Chinese folk for centuries. Our laboratory previously demonstrated that Ganoderma lucidum polysaccharides (GLPs) had hypoglycemic effects in diabetic mice. Our aim was to identify the main bioactives in GLPs and corresponding mechanism of action.
Materials and methods:
Four polysaccharide-enriched fraction were isolated from GLPs and the antidiabetic activities were evaluated by type 2 diabetic mice. Fasting serum glucose (FSG), fasting serum insulin (FSI) and epididymal fat/BW ratio were measured at the end of the experiment. In liver, the mRNA levels of hepatic glucose regulatory enzymes were determined by quantitative polymerase chain reaction (qPCR) and the protein levels of phospho-AMP-activated protein kinase (p-AMPK)/AMPK were determined by western blotting test. In epididymal fat tissue, the mRNA and protein levels GLUT4, resistin, fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC1) were determined by qPCR and immuno-histochemistry. The structure of polysaccharide F31 was obtained from GPC, FTIR, NMR and GC-MS spectroscopy, RESULTS: F31 significantly decreased FSG (P<0.05), FSI and epididymal fat/BW ratio (P<0.01). In liver, F31 decreased the mRNA levels of hepatic glucose regulatory enzymes, and up-regulated the ratio of phospho-AMP-activated protein kinase (p-AMPK)/AMPK. In epididymal fat tissue, F31 increased the mRNA levels of GLUT4 but decreased fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC1) and resistin. Immuno-histochemistry results revealed F31 increased the protein levels of GLUT4 and decreased resistin.
Conclusion:
Data suggested that the main bioactives in GLPs was F31, which was determined to be a β-heteropolysaccharide with the weight-average molecular weight of 15.9kDa. The possible action mechanism of F31 may be associated with down-regulation of the hepatic glucose regulated enzyme mRNA levels via AMPK activation, improvement of insulin resistance and decrease of epididymal fat/BW ratio. These results strongly suggest that F31 has antidiabetic potential.
Prebiotics alter bacterial content in the colon, and therefore could be useful for obesity management. We investigated the changes following addition of inulin oligofructose (IO) in the food of rats fed either a corn starch (C) diet or a high-carbohydrate, high-fat (H) diet as a model of diet-induced metabolic syndrome. IO did not affect food intake, but reduced body weight gain by 5·3 and 12·3 % in corn starch+inulin oligofructose (CIO) and high-carbohydrate, high-fat with inulin oligofructose (HIO) rats, respectively. IO reduced plasma concentrations of free fatty acids by 26·2 % and TAG by 75·8 % in HIO rats. IO increased faecal output by 93·2 %, faecal lipid excretion by 37·9 % and weight of caecum by 23·4 % and colon by 41·5 % in HIO rats. IO improved ileal morphology by reducing inflammation and improving the density of crypt cells in HIO rats. IO attenuated H diet-induced increases in abdominal fat pads (C 275 (sem 19), CIO 264 (sem 40), H 688 (sem 55), HIO 419 (sem 32) mg/mm tibial length), fasting blood glucose concentrations (C 4·5 (sem 0·1), CIO 4·2 (sem 0·1), H 5·2 (sem 0·1), HIO 4·3 (sem 0·1) mmol/l), systolic blood pressure (C 124 (sem 2), CIO 118 (sem 2), H 152 (sem 2), HIO 123 (sem 3) mmHg), left ventricular diastolic stiffness (C 22·9 (sem 0·6), CIO 22·9 (sem 0·5), H 27·8 (sem 0·5), HIO 22·6 (sem 1·2)) and plasma alanine transaminase (C 29·6 (sem 2·8), CIO 32·1 (sem 3·0), H 43·9 (sem 2·6), HIO 33·6 (sem 2·0) U/l). IO attenuated H-induced increases in inflammatory cell infiltration in the heart and liver, lipid droplets in the liver and plasma lipids as well as impaired glucose and insulin tolerance. These results suggest that increasing soluble fibre intake with IO improves signs of the metabolic syndrome by decreasing gastrointestinal carbohydrate and lipid uptake.
Retention of phenolic compounds during spray-drying of an anti-diabetic C. subternata extract and physicochemical characteristics of spray-dried powders (pure extract and extract-carrier mixtures) were evaluated. Extract-carrier mixtures contained three levels (250, 500 and 750 g/kg) of the microencapsulating agents, namely corn syrup solids, commonly used by the food industry, and inulin, a low-kilojoule alternative. The amorphous spray-dried powders ranged from nearly free-flowing to cohesive. Their moisture content and water activity fell within the range of their monolayer moisture values. The moisture sorption isotherm of the pure extract showed very little hysteresis, contrary to the mixtures containing carriers. Similar values for calculated and experimental heat flow, determined by isothermal microcalorimetry, indicated the carriers to be compatible with the extract, except when used in a mixture containing 750 g/kg corn syrup solids. Spray-drying had no detrimental effect on the individual phenolic content, in particular the heat labile mangiferin, isomangiferin and 3-β-D-glucopyranosyliriflophenone, and the total antioxidant capacity of the extract. Microencapsulation of C. subternata extract with inulin by spray-drying thus provides a stable low-kilojoule powder, suitable for formulation of single-serve beverage mixtures that can be used by diabetics.
Ethnopharmacological relevance:
Liuwei Dihaung decoction(LWDHT) is a well-known classic traditional Chinese medicine formula, consists of six herbs including Rehmannia glutinosa Libosch.(family: Scrophulariaceae), Cornus officinalis Sieb.(family: Cornaceae), Dioscorea opposite Thunb.(family:Dioscoreaceae), Alisma orientale(G.Samuelsson) Juz (family: Alismataceae),Poria cocos (Schw.) Wolf (family: Polyporaceae) and Paeonia suffruticosa Andrews (family: Paeoniaceae). It has been used in the treatment of many types of diseases with signs of deficiency of Yin in the kidneys in China clinically. This study is aimed at investigating the effect of Liuwei dihuang decoction on PI3K/Akt signaling pathway in liver of T2DM rats with insulin resistance.
Materials and methods:
T2DM model was induced by high sugar and high fat diet in combination with small dose of streptozocin (STZ) injection in male Sprague-Dawley (SD) rats.The successful T2DM rats were randomly divided into three group--vehicle group，positive control group and Liuwei Dihuang decoction group. After 12 weeks of treatment with distilled water, rosiglitazone and LWDH by intragastric administration respectively, the rats were put to death in batch. The changes of fasting blood glucose (FBG), fasting insulin (FINS) in serum were determined, the pathological changes of each rats' liver were observed by hematoxylin-eosin (HE) staining, the expression of insulin receptor substrate 2(IRS2), phosphatidylinositol 3-kinase (PI3K) and protein kinas B (Akt) involving the canonical PI3K/Akt signaling pathway were detected by Real-time fluorescent quantitative PCR (RT-PCR), and the expression level of IRS2, PI3K, Akt protein and phosphorylated IRS2, PI3K, Akt protein were detected by Western Blot. All the data were analyzed by SPSS 17.0.
Results:
Four weeks of treatment with LWDHT could significantly decrease the level of FBG and FINS in serum, improve the cellular morphology of liver, kidney, pancreas tissue, and the expression of IRS2, PI3K, Akt mRNA and phosphorylated IRS2, PI3K, Akt protein involved in the canonical PI3K/Akt signaling pathway of T2DM rats in liver were significantly up-regulated, while the total IRS2, PI3K, and Akt protein had no obvious changes.
Conclusions:
Our results suggest that Liuwei Dihuang decoction could intervene insulin resistance of T2DM, in part, through regulation of canonical PI3K/Akt signaling pathway of T2DM rats in liver.
Herein, we investigated the hypoglycemic effect of plant gallic acid (GA) on glucose uptake in an insulin-resistant cell culture model and on hepatic carbohydrate metabolism in rats with a high-fructose diet (HFD)-induced diabetes. Our hypothesis is that GA ameliorates hyperglycemia via alleviating hepatic insulin resistance by suppressing hepatic inflammation and improves abnormal hepatic carbohydrate metabolism by suppressing hepatic gluconeogenesis and enhancing the hepatic glycogenesis and glycolysis pathways in HFD-induced diabetic rats. Gallic acid increased glucose uptake activity by 19.2% at a concentration of 6.25μg/mL in insulin-resistant FL83B mouse hepatocytes. In HFD-induced diabetic rats, GA significantly alleviated hyperglycemia, reduced the values of the area under the curve for glucose in an oral glucose tolerance test, and reduced the scores of the homeostasis model assessment of insulin resistance index. The levels of serum C-peptide and fructosamine and cardiovascular risk index scores were also significantly decreased in HFD rats treated with GA. Moreover, GA up-regulated the expression of hepatic insulin signal transduction-related proteins, including insulin receptor, insulin receptor substrate 1, phosphatidylinositol-3 kinase, Akt/protein kinase B, and glucose transporter 2, in HFD rats. Gallic acid also down-regulated the expression of hepatic gluconeogenesis-related proteins, such as fructose-1,6-bisphosphatase, and up-regulated expression of hepatic glycogen synthase and glycolysis-related proteins, including hexokinase, phosphofructokinase, and aldolase, in HFD rats. Our findings indicate that GA has potential as a health food ingredient to prevent diabetes mellitus.
Presently, an efficient protein tyrosine phosphatase 1B (PTP1B) inhibitor, named FYGL-n, was isolated from Ganoderma Lucidum and characterized for its structure and bioactivity. Structure and chain conformation of FYGL-n based on both chemical and spectroscopic analysis showed that FYGL-n was a hyperbranched heteropolysaccharide bonded with protein via both serine and threonine residues by O-type glycoside, and showed a sphere observed by AFM. Specifically, monosaccharide composition indicated that FYGL-n consisted of d-arabinose, d-galactose, l-rhamnose and d-glucose in a mole ratio of 0.08:0.21:0.24:0.47, with a molecular mass of 72.9 kDa. The analysis of amino acids in FYGL-n indicated that there were 16 common amino acids, among which aspartic acid, glycine, serine, alanine, glutamic acid and threonine were the dominant components. Also it was demonstrated that FYGL-n could inhibit the PTP1B activity on a competitive mechanism in vitro.
Compound K (CK) is a final metabolite of panaxadiol ginsenosides from Panax ginseng. Although anti-diabetic activity of CK has been reported in recent years, the molecular mechanism of CK in the treatment of diabetes mellitus remains unclear. In the present investigation, we established a rat model of type 2 diabetes mellitus (T2DM) with insulin resistance using high-fat diet (HFD) and streptozotocin (STZ), and attempted to verify more details and exact mechanisms in the treatment of T2DM. CK was administered orally at three doses [300, 100 and 30 mg/kg bodyweight (b.w.)] to the diabetic rats. Bodyweight, food-intake, fasting blood glucose (FBG), fasting serum insulin (FINS), insulin sensitivity (ISI), total glycerin (TG), total cholesterol (TC), as well as oral glucose tolerance test (OGTT) were evaluated in normal and diabetic rats. According to our results, CK could improve bodyweight and food-intake of diabetic rats. CK exhibited dose-dependent reduction of FBG, TG and TC of diabetic rats. CK treatment also enhanced FINS and ISI. Meanwhile, the glucose tolerance observed in the present study was improved significantly by CK. It is concluded from the results that CK may have improving effects on hyperglycemia and insulin resistance of diabetic rats. Furthermore, the research showed CK could promote the expression of InsR, IRS1, PI3Kp85, pAkt and Glut4 in skeletal muscle tissue of diabetic rats. These results indicate that the hypoglycemic activity of CK is mediated by improving of insulin sensitivity, which is closely related to PI3K/Akt signaling pathway.
A polysaccharide from Ganoderma atrum (PSG-1) was purified and characterized, and its hypoglycemic and hypolipidemic effects were investigated in high fat diet- and streptozotocin-induced type 2 diabetic rats. Oral administration of PSG-1 at 200 or 400mg/kg body weight significantly reduced fasting blood glucose and serum insulin levels. PSG-1 significantly decreased the levels of serum total cholesterol, triglyceride, high-density lipoprotein cholesterol, free fatty acid and insulin resistance, and increased low-density lipoprotein cholesterol level and insulin sensitivity. In addition, PSG-1 inhibited the expression of pro-apoptotic protein, Bax and increased the expression of anti-apoptotic protein, Bcl-2 in pancreatic cells, suggesting that PSG-1 exerted a protective role in the pancreas of diabetic rats. These results indicated that PSG-1 may have a potential for the treatment of hyperglycemia, hyperlipidemia, hyperinsulinemia and insulin resistance in type 2 diabetes.
Our aims were to investigate the hypoglycemic effects and mechanisms of action of Ganoderma lucidum polysaccharides (GLPs) administered for 7 days in type 2 diabetic mice. The mice were randomly divided into four groups (8 mice/group): normal control group, diabetic control group, low-dose GLP-treated diabetic group (50 mg/kg/d), and high-dose GLP-treated diabetic group (100 mg/kg/d). Diabetes was induced by streptozotocin injection and high-fat dietary feeding. At the end of the study, fasting serum glucose, insulin, body weight (BW) and epididymal white adipose tissue weight were measured. The hepatic mRNA levels of glycogen phosphorylase (GP), fructose-1,6-bisphosphatase (FBPase), phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) genes were determined by real-time polymerase chain reaction. Both doses of GLPs significantly decreased fasting serum glucose, insulin and epididymal fat/BW ratio compared with the diabetic control group (p < 0.05). The hepatic mRNA levels of GP, FBPase, PEPCK and G6Pase were significantly lower in both GLP-treated groups compared with the diabetic control group. Taken together, GLPs significantly decrease fasting serum glucose levels in type 2 diabetic mice in a dose-dependent manner. The decreases in fasting serum glucose levels may be associated with decreased mRNA expression levels of several key enzymes involved in gluconeogenesis and/or glycogenolysis.
Previous studies have demonstrated that Ganoderma lucidum polysaccharides (Gl-PS) exhibited potential antihyperglycemic effect in rats. The aim of the present study was to investigate the mechanism of the hypoglycemic effect of a low- molecular-weight Gl-PS in streptozotocin (STZ)-induced diabetic Sprague-Dawley (SD) rats. Gl-PS was extracted and purified from Ganodema lucidum fruiting body. 50 male SD rats were included in the study; 10 were taken as healthy controls; 40 were induced to diabetes by a single injection of 65 mg/kg STZ, of which 30 were selected as successful diabetic rat models. The 30 diabetic rats were divided into three groups: Gl-PS (200 mg/kg Gl-PS), metformin (100 mg/kg metformin) and diabetic control (n = 10 per group). After eight weeks' oral administration, plasma concentrations of fasting glucose, triacylglyceride, total cholesterol and nitric oxide were significantly decreased in Gl-PS and metformin groups. Pancreatic superoxide dismutase, catalase and glutathione peroxidase were significantly increased in Gl-PS and metformin groups. Histopathological results showed that Gl-PS and metformin had protective effect on β-cells. The mRNA expressions of Bcl-2 and PDX-1 in pancreas were up-regulated, but Bax, iNOS and Casp-3 down-regulated in Gl- PS and metformin groups compared to diabetic control group. The present results suggested that Gl-PS had a hypoglycemic effect in STZ-induced diabetic rats through preventing apoptosis of pancreatic β-cells and enhancing β-cells regeneration.
The intake of 10 g/day of short-chain-fructo-oligosaccharides (sc-FOS) has been shown to increase significantly bifidus counts and to produce high amounts of short-chain fatty acids (SCFA), presumed to influence glucose and lipid metabolism.
To evaluate the effects of moderate intake of sc-FOS on glucose and lipid metabolism in individuals with mild hypercholesterolaemia. Design: A randomized double-blind sequential cross-over study.
Thirty subjects of both genders (20 M/10 F), mean age 45.5+/-9.9 years (M+/-SD), BMI 26.6+/-2.2 kg/m(2), with plasma cholesterol >5.17 and <7.76 mmol/l and plasma triglycerides <3.45 mmol/l, participated in the study. The study was performed after a wash-out period of 1 month and a run-in period of 1 month to stabilize patients on a standard diet (CHO 50%, fat 30%, protein 20%, fibre 20 g/day) plus placebo (maltodextrine plus aspartame 15 g/day). At the end of run-in, subjects were randomly assigned to receive sc-FOS (Actilight) (10.6g/day) or placebo (maltodextrine plus aspartame 15 g/day) with tea and/or coffee for a duration of 2 months and thereafter switched to the other treatment for additional 2 months. Plasma glucose, total and lipoprotein (VLDL, LDL, HDL) cholesterol and triglyceride concentrations were measured in the fasting state at the end of run-in and of each treatment period. At the end of the two treatment periods, patients consumed a standard test meal (protein 15%, carbohydrate 34%, fat 51%, kJ 3988) 1h after the administration of 5.3g of sc-FOS or placebo; plasma glucose, insulin, free fatty acid (FFA) and triglyceride responses to the test meal were evaluated.
No significant difference in fasting parameters was detected between the two treatments. After sc-FOS and placebo plasma cholesterol levels were, respectively, 6.47+/-0.70 and 6.44+/-0.78 mmol/l (n.s.) and plasma triglycerides were 1.53+/-0.71 and 1.56+/-0.53 mmol/l (n.s.). No significant differences were observed in cholesterol and triglyceride content of VLDL, LDL and HDL and in plasma Apo A1 levels; conversely, fasting plasma Lp(a) concentrations were significantly increased after sc-FOS (37+/-38 vs. 33+/-35 mg/dl; P<0.005). Postprandial responses of glucose, FFA and triglycerides were not significantly different between sc-FOS and placebo, while postprandial insulin response (incremental area) was significantly reduced after sc-FOS compared to placebo (14,490+/-7416 vs. 17,760+/-7710 pmol/l x 300 min; P<0.02).
A moderate intake of sc-FOS has no major effects on lipid metabolism, both in the fasting and in the postprandial period, in individuals with mild hypercholesterolaemia. A small but significant increase of Lp(a) concentrations was observed with sc-FOS consumption together with a reduction of the postprandial insulin response; however, the clinical relevance of these small effects is unclear.