Article

Effects of marine collagen peptides on glucose metabolism and insulin resistance in type 2 diabetic rats

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Abstract

The present study was conducted to investigate the effects of marine collagen peptides (MCPs) on glucose metabolism and insulin resistance using a rat model of type 2 diabetes mellitus (T2DM). Forty T2DM obese Wistar rats were randomly assigned to receive varying doses of MCPs or a vehicle control for 4 weeks. Blood glucose and insulin levels, as well as oxidative stress and inflammation were measured. The expression of glucose transporter type 4 (GLUT4) in skeletal muscles and peroxisome proliferator-activated receptor-α (PPAR-α) in livers of T2DM rats was also measured. It was found that in the group of 9.0 g/kg/day MCPs significantly improved glucose, insulin, and homeostatic model assessment-insulin resistance, and increased the insulin sensitivity index (ISI). In addition, the groups of 4.5 and 2.25 g/kg/day MCPs significantly improved liver steatosis. It was also found that MCPs decreased expression of oxidative stress biomarkers and inflammatory cytokines and adipocytokines in T2DM rats. In conclusion, medium and high doses of MCPs (≥4.5 g/kg/day) improved glucose metabolism and insulin sensitivity in T2DM rats. These beneficial effects of MCPs may be mediated by decreasing oxidative stress and inflammation and by up-regulating GLUT4, and PPAR-α activity.

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... When present in injectable gel formulations and/or in dietary supplements, MC contributes to reduce the risk of joint deterioration and inflammation [172,173]. Interestingly, recent studies also suggest the potential of ingested MC or MC fragments for weight management [174,175] and glycemic control [176][177][178]. Finally, MC represents a useful source of various antimicrobial peptides [179]. ...
... In particular, the peroxisome proliferator activated receptor-α (PPAR-α) was significantly expressed. This nuclear hormone receptor plays an important role in the modulation of insulin sensitivity, besides functioning as a lipid sensor that controls fatty acids burn [178]. Thus, its overexpression led to an increase of the fatty acid metabolism and then fats burn. ...
... As a cascade of events the oxidative stress, the activity of the glucose transporter type 4 (GLUT-4) and the PPAR-α activity are all implicated in the pathogenesis of insulin resistance [177,206,218,219]. Orally administered MC peptides have been found to reduce oxidative stress, inflammation, and modulated GLUT-4 and PPAR-α expression in rat models of T2D [178]. PPAR-α expression in the liver of diabetic rats suggests that MC peptides can act on diabetes by enhancing insulin sensitivity. ...
Article
In the last two decades, marine collagen has attracted great scientific and industrial interest as a ‘blue resource’, with potential for use in various health-related sectors, such as food, medicine, pharmaceutics and cosmetics. In particular, the large availability of polluting by-products from the fish processing industry has been the key factor driving the research towards the conversion of these low cost by-products (e.g. fish skin and scales) into collagen-based products with high added value and low environmental impact. After addressing the extraction of collagen from aquatic sources and its physicochemical properties, this review focuses on the use of marine collagen and its derivatives (e.g. gelatin and peptides) in different healthcare sectors. Particular attention is given to the bioactive properties of marine collagen that are being explored in preclinical and clinical studies, and pave the way to an increased demand for this biomaterial in the next future. In this context, in addition to the use of native collagen for the development of tissue engineering or wound healing devices, particularly relevant is the use of gelatin and peptides for the development of dietary supplements and nutraceuticals, specifically directed to weight management and glycemic control. The marine collagen market is also briefly discussed to highlight the opportunities and the most profitable areas of interest.
... tissue repair in burns (15), diabetes (16) and aging (17). It has been suggested that collagen also has anti-inflammatory, anti-oxidant, and anti-diabetic properties (18)(19)(20) in excisional wounds and other experimental models, which have not yet been investigated in burns. Omega-3 fatty acids (FAs) are other important nutrients with anti-inflammatory properties, which were reported to be advantageous in reduction of infection, sepsis, and septic shock (21,22), as well as decreasing hospital (21) and intensive care unit (23) stay in burns. ...
... There was a decrease in oxidative stress (higher SOD, GPx, NO, and lower malondialdehyde (MDA)) and inflammation (lower tumor necrosis factor α, CRP, interferon γ) in the intervention compared to the control group. Most effects were observed in medium and high doses of the supplement but CRP levels decreased even with low doses of collagen (20). Collectively, the beneficial effects of collagen on inflammation and metabolic control might be due to its anti-inflammatory, anti-oxidant, and anti-diabetic properties, as well as the specific amino acid content of this protein. ...
Article
Introduction: Collagen and omega-3 fatty acids (FAs) are suggested to have anti-inflammatory, anti-oxidant, and insulin-sensitizing properties. The aim of this study was to investigate the effect of collagen hydrolysate and omega-3 FAs on inflammation and insulin resistance in patients with major burns. Methods: In this double-blind randomized clinical trial, 66 patients with 20-45% burns were assigned to either of the three groups of collagen (40 gr/d), collagen (40 gr/d) plus fish oil (10 ml/d), or control. High-sensitivity C-reactive protein (hs-CRP), fasting blood glucose (FBG) and insulin concentrations, and homeostatic model assessment for insulin resistance (HOMA-IR) were assessed at baseline, as well as end of weeks two and three. Results: Based on post-hoc analyses, hs-CRP levels were significantly lower in the collagen (p=0.026) and collagen+omega-3 (p=0.044) groups compared to the control group, at week three. However, pre- to post- (week three) changes of hs-CRP were significantly higher only in the collagen+omega-3 group compared to the control group (173.2 vs. 103.7 mg/l, p=0.024). After three weeks of the intervention, insulin (11.3 and 11.9 vs. 22.8 µIU/ml) and HOMA-IR (2.9 and 2.8 vs. 7.9) values seemed to be clinically, but not statistically, lower in both intervention groups compared to the control group. Pre- to post- (week three) values of FBG decreased significantly in the collagen (p=0.002) and collagen+omega-3 (p=0.036) groups. Insulin (p=0.008) and HOMA-IR (p=0.001) decreased significantly only in the collagen+omega-3 group at week three compared to the baseline. Conclusions: Supplementation with collagen hydrolysate and omega-3 FAs can improve hs-CRP concentration and probably insulin resistance in patients with severe burns. Omega-3 FAs had additional effects on modulating inflammation. Larger clinical trials are needed to confirm the current findings especially in terms of glucose homeostasis.
... Similarly, the collagen derived from salmon [31], gray mullet [5], and skate [22] exert plasma lipid-lowering effects. In addition, chum salmon skin-derived collagen peptide increases adiponectin and decreases leptin levels in rats [32]. Similarly, the results of this study indicate that SSCP could have partial effects on regulation of the leptin level, indicating that both LCP and HCP lowers leptin levels. ...
... As a result, the LCP-fed groups had lower hepatic TG and TC levels, as evidenced by the histological results, demonstrating that hepatic lipid deposits were suppressed. These results are consistent with a previous study showing that collagen peptide derived from chum salmon skin prevented liver steatosis by upregulating PPARα expression in rats [32]. Our previous study demonstrated the dose-dependent effects of skate skin collagen peptide (without ultrafiltration) on the reduction of the hepatic lipid concentration mediated through the regulation of lipid metabolism-related genes in diet-induced obese mice [20]. ...
Article
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This study investigated the effects of skate skin collagen peptide (SSCP) with different molecular weights (MWs) on the lipid metabolism in the liver and adipose tissue. Male db/db mice were orally administered with water (control group) or low SSCP (LCP group) or high SSCP (HCP group) MW for 8 weeks whereas male m/m mice were used for comparison (normal group) (n = 10 each group). Compared to the control group, the LCP and HCP groups had lower adipose tissue mass, plasma and hepatic lipid concentrations, and plasma leptin levels (p < 0.05). Protein expression levels of lipogenesis-related protein were reduced in both liver and adipose tissues of SSCP-fed groups whereas those for lipolysis were elevated (p < 0.05). In particular, the LCP had the higher effects relative to the HCP. The above results were supported by histological analysis, revealing that SSCP administration decreased the size of adipose droplets and suppressed hepatic lipid accumulation. Our results showed that SSCP has potential antiobesity properties through the improvement of lipid metabolism in the liver and adipose tissue; in particular, the lower MW of collagen peptide had the greater effects.
... Similarly, the abundant Pro and Ala were detected at the penultimate C-terminal sequence of the peptides. Additionally, many peptides such as PLV (Kwak et al., 2016), IPPKKNQDKTE (Song et al., 2017), IRW (Zhu et al., 2017), ERPIL (Jahandideh, Liu, & Wu, 2018) and VFKGL (Jahandideh et al., 2018) were proved to have insulin resistance ameliorating effect. These peptides generally consisted of abundant Pro and Leu/Ile at the C-end and/ or N-end. ...
Article
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In this study, anti-diabetic activity and potential mechanism of sea cucumber hydrolysates (SCH) were investigated in type II diabetic rats induced by streptozotocin. Results showed that SCH alleviated body weight loss, oral glucose tolerance and insulin resistance in diabetic rats. The fasting blood glucose level was markedly decreased by 40.39% after SCH administration. Moreover, lipid metabolism disorders in diabetic rats were attenuated to near normal after SCH treatment. Mechanism studies showed that the expressions of PI3K, p-Akt, p-GSK-3β and GLUT2/GLUT4 were significantly increased and the expression of p-IRS1 was significantly decreased after SCH treatment in liver and skeletal muscle tissues of diabetic rats. In addition, 25 peptides were screened as potential bioactive peptides by analyzing the intensity of mass spectra combined with PeptideRanker prediction. In summary, these findings suggested that SCH improved insulin resistance in diabetic rats via triggering PI3K/Akt signaling pathway, indicating that SCH may possess anti-diabetic effects.
... Marine collagen peptides are known to exhibit range of bioactivities-immune stimulant (Yang et al., 2009), antioxidant (Ding et al., 2011;Liang et al., 2010), anti-cancerous (Hsu, Li Chan, & Lao, 2011), ace-inhibition (Gu, Li, Liu, Yi, & Cai, 2011;Kim et al., 2011), antidiabetic, antihypertensive and anti-arthritic (Moskowitz, 2000). Various researchers have suggested beneficial role of MCPs in alleviating age-related memory deficits , wound healing (Wang et al., 2015;Yang, Zhang, Li, & Hou, 2018), glucose metabolism, insulin resistance (Zhu et al., 2017) and preventing age-related bone loss (Konig, Oesser, Scharla, Zdzieblik, & Gollhofer, 2018). ...
Article
Marine collagen peptide (MCP), usually obtained from the scales/skin of fish is a promising functional component possessing various health benefits. An attempt was made to indicate the potential application of MCP as dietary supplement. MCP was incorporated (0–10%) in the biscuit flour and its effects on physical, textural and sensorial behaviour of biscuits were assessed. The functional properties of MCP-flour mix were also evaluated. Water holding capacity was significantly (p < 0.05) decreased by the addition of MCP whereas no significant effect was observed on oil absorption capacity. Further, incorporation led to decrease (p < 0.05) in all gelatinization-viscosity parameters (peak, trough, breakdown, final and setback viscosity). Significant appreciation (p < 0.05) in protein and antioxidative potential along with a slight decrease (p < 0.05) in calorie content of biscuits, was observed upon supplementation. A concentration dependent increase was observed in the spread ratio of biscuits upon fortification with MCP. Addition of MCP also caused significant reduction in lightness value and increased content of Mailard reaction products, as exhibited by browning intensity (p < 0.05). Nutritionally improved collagen peptide biscuits were sensorially preferred (liked moderately-very much) by the sensory panelists. Further, functionality of MCP could be utilized for human health by incorporation in other appropriate food systems. These foods can serve as a potential option in geriatric nutrition.
... These results suggest that MCPs may be a novel therapeutic tools to protect against early cardiovascular complications associated with T2DM. In line with these results, MCPs were found to improve glucose metabolism and insulin resistance, to decrease the expression of oxidative stress biomarkers and inflammatory cytokines and adipocytokines in livers of T2DM rat models [166]. ...
Article
Full-text available
This review focuses on the expanding role of marine collagen (MC)-based scaffolds for biomedical applications. A scaffold—a three-dimensional (3D) structure fabricated from biomaterials—is a key supporting element for cell attachment, growth, and maintenance in 3D cell culture and tissue engineering. The mechanical and biological properties of the scaffolds influence cell morphology, behavior, and function. MC, collagen derived from marine organisms, offers advantages over mammalian collagen due to its biocompatibility, biodegradability, easy extractability, water solubility, safety, low immunogenicity, and low production costs. In recent years, the use of MC as an increasingly valuable scaffold biomaterial has drawn considerable attention from biomedical researchers. The characteristics, isolation, physical, and biochemical properties of MC are discussed as an understanding of MC in optimizing the subsequent modification and the chemistries behind important tissue engineering applications. The latest technologies behind scaffold processing are assessed and the biomedical applications of MC and MC-based scaffolds, including tissue engineering and regeneration, wound dressing, drug delivery, and therapeutic approach for diseases, especially those associated with metabolic disturbances such as obesity and diabetes, are discussed. Despite all the challenges, MC holds great promise as a biomaterial for developing medical products and therapeutics.
... reduced aortic plaque area, as seen by én-face analysis. The mechanism behind this effect is unclear, but Zhu et al. have shown that marine peptides may act as peroxisome proliferator-activated receptor ligands (PPAR) and exert anti-inflammatory effects (Zhu et al., 2010(Zhu et al., , 2017). ...
Article
Full-text available
Chicken protein hydrolysates (CPHs) generated from rest raw materials through enzymatic hydrolysis using Corolase PP or Alcalase were shown to reduce inflammation and stimulate hepatic mitochondrial fatty acid oxidation in high‐fat‐fed mice. This study investigates the effect of CPH diets in atherosclerosis‐prone apolipoprotein E‐deficient (Apoe−/−) mice. Apoe−/− mice were divided into three groups of 12 animals and fed high‐fat diets with casein (control), Alcalase CPH, or Corolase PP CPH. After 12 weeks, mice were sacrificed, blood samples were collected, and aorta was dissected for subsequent én face analysis. Mice fed Corolase PP CPH but not Alcalase CPH had significantly lower % atherosclerotic plaque area in the aortic arch compared to controls (p = .015 and p = .077, respectively). Plasma and liver cholesterol and triacylglycerol remained constant, but levels of the fatty acid C20:5n‐3 were increased, accompanied by an elevated delta‐5 desaturase index in both CPHs groups. Moreover, a significant reduction of plasma MCP‐1 was detected in Corolase PP CPH compared to control. Overall, our data show that protein hydrolysates from chicken reduced atherosclerosis and attenuated systemic risk factors related to atherosclerotic disorders, not related to changes in the level of plasma cholesterol. Chicken protein hydrolysates (CPHs) generated from rest raw materials through enzymatic hydrolysis using Corolase PP or Alcalase were shown to reduce aortic atherosclerotic plaque formation compared to a casein control in Apoe‐/‐ mice fed a high‐fat diet for 12 weeks. This reduction was independent of plasma lipid levels, but may be linked to effects on fatty acid composition and systemic inflammatory processes.
... The DPP-4 inhibition property of collagen peptide has great relevance as a natural source for management of T2DM through incretin effect. There are several in vitro [10][11][12] and studies in animal models [13][14][15] and human clinical trials [16][17][18] on hypoglycaemic effect of collagen derived peptides, by making use of its ability to inhibit DPP-4. The US patent by Sugihara et al. [19] describes the potential role of peptides derived from collagen as the therapeutic or preventive agent for diabetes. ...
Article
Full-text available
Dipeptidyl peptidase-4 (DPP-4) inhibitors constitute an innovative class of oral agents for the treatment of Type 2 Diabetes Mellitus (T2DM). DPP-4 inhibitors increase glucagon-like peptide-1 (GLP-1) availability and correct the "incretin defect" seen in T2DM patients. Peptides derived from collagen have been reported to have DPP-4 inhibitory properties. A double blind randomized trial has been conducted to evaluate the effectiveness of Collagen peptides (CPT) as nutritional supplement in subjects with T2DM. Resistant dextrin (RD), a non-digestible dietary polymer, has been used as active comparator in this study. The clinical study was conducted over a total duration of 12 weeks of treatment period. The study was conducted on 66 enrolled subjects randomized in a 2:2:1:1 ratio as a four arm clinical study design. The subjects consumed either CPT (2.5/5 g) or resistant dextrin (2.5/5 g) for 90 days. The results showed that the consumption of 5 g CPT resulted in significant reduction in fasting blood glucose (FBG) and Glycosylated Haemoglobin (HbA1c) in three months study period in subjects. Insulin sensitivity measured in as HOMA IR has also been improved significantly in the group. Thus this study demonstrates the potential role of CPT as add on nutritional supplement for the management of T2DM.
... The DPP-4 inhibition property of collagen peptide has great relevance as a natural source for management of T2DM through incretin effect. There are several in vitro [10][11][12] and studies in animal models [13][14][15] and human clinical trials [16][17][18] on hypoglycaemic effect of collagen derived peptides, by making use of its ability to inhibit DPP-4. The US patent by Sugihara et al. [19] describes the potential role of peptides derived from collagen as the therapeutic or preventive agent for diabetes. ...
... The DPP-4 inhibition property of collagen peptide has great relevance as a natural source for management of T2DM through incretin effect. There are several in vitro [10][11][12] and studies in animal models [13][14][15] and human clinical trials [16][17][18] on hypoglycaemic effect of collagen derived peptides, by making use of its ability to inhibit DPP-4. The US patent by Sugihara et al. [19] describes the potential role of peptides derived from collagen as the therapeutic or preventive agent for diabetes. ...
... Salmon protein hydrolysates were shown to stimulate insulin-induced glucose uptake in L6 myocytes ( Jin, 2012). Salmon skin gelatin derived peptides were reported to reduce blood glucose concentrations in diabetic rat models through enhancement of circulating GLP-1 concentration and reduction in T2DM-related islet cell apoptosis ( Hsieh, Wang, Hung, C., & Hsu, 2012;Zhu et al., 2017;Zhu, Peng, Liu, Zhang, & Li, 2010). Salmon protein incorporation into a high-fat, high-sucrose diet was shown to improve whole-body insulin sensitivity and glucose tolerance in male Wistar rats ( Pilon et al., 2011). ...
Article
Large quantities of low-value protein rich co-products, such as salmon skin and trimmings, are generated annually. These co-products can be upgraded to high-value functional ingredients. The aim of this study was to assess the antidiabetic potential of salmon skin gelatin and trimming-derived protein hydrolysates in vitro. The gelatin hydrolysate generated with Alcalase 2.4 L and Flavourzyme 500 L exhibited significantly higher (p < .001) insulin and GLP-1 secretory activity from pancreatic BRIN-BD11 and enteroendocrine GLUTag cells, respectively, when tested at 2.5 mg/mL compared to hydrolysates generated with Alcalase 2.4 L or Promod 144MG. The gelatin hydrolysate generated with Alcalase 2.4 L and Flavourzyme 500 L showed significantly more potent (p < .01) DPP-IV inhibitory activity than those generated with Alcalase 2.4 L or Promod 144MG. No significant difference was observed in the insulinotropic activity mediated by any of the trimming-derived hydrolysates when tested at 2.5 mg/mL. However, the trimmings hydrolysate generated with Alcalase 2.4 L and Flavourzyme 500 L exhibited significantly higher DPP-IV inhibitory (p < .05:Alcalase 2.4 L and p < .01:Promod 144MG) and GLP-1 (p < .001, 2.5 mg/mL) secretory activity than those generated with Alcalase 2.4 L or Promod 144MG. The salmon trimmings hydrolysate generated with Alcalase 2.4 L and Flavourzyme 500 L when subjected to simulated gastrointestinal digestion (SGID) was shown to retain its GLP-1 secretory and DPP-IV inhibitory activities, in addition to improving its insulin secretory activity. However, the gelatin hydrolysate generated with Alcalase 2.4 L and Flavourzyme 500 L was shown to lose GLP-1 secretory activity following SGID. A significant increase in membrane potential (p < .001) and intracellular calcium (p < .001) by both co-product hydrolysates generated with Alcalase 2.4 L and Flavourzyme 500 L suggest that both hydrolysates mediate their insulinotropic activity through the KATP channel-dependent pathway. Additionally, by stimulating a significant increase in intracellular cAMP release (p < .05) it is likely that the trimming-derived hydrolysate may also mediate insulin secretion through the protein kinase A pathway. The results presented herein demonstrate that salmon co-product hydrolysates exhibit promising in vitro antidiabetic activity.
... Recent studies also reveal the potential of CPs to improve glucose and lipid metabolism. A high dose (4.5 g/kg body weight/d) of CPs derived from marine fi shes could improve glucose metabolism and reduce insulin resistance in type-2 diabetes rats (16). CPs also inhibit dipeptidyl peptidase-IV and stimulate glucagonlike-peptide-1 (GLP-1) secretion. ...
Article
Collagen peptides (CPs) are bioactive molecules that have beneficial effects on bone metabolism and against joint disorders. In the present study, we investigated the effect of CP supplementation on visceral fat mass and plasma lipid concentrations in high-fat diet (HFD)-induced obese mice. Male ddY mice were fed a normal diet or HFD for 3 wk, and assigned to N or NCP groups and to F or FCP groups, respectively. The NCP and FCP group mice were administered experimental diets containing 25 mg/g CPs for 3 wk further. During the experimental period, CP supplementation affected neither the food consumption nor the body weight of the mice. No significant differences in the plasma triglyceride, non-esterified fatty acid, and cholesterol concentrations were observed among all the groups. In contrast, the weight of testicular fat mass was significantly decreased in the FCP group as compared with that in the F group. The expression levels of leptin and tumor necrosis factor (TNF)-α genes in the adipose tissue correlated with the visceral fat mass, although these differences were not significant. These findings indicate that CPs may have a reducing effect on visceral fat content but are less effective in reducing body weight.
... It has been reported that it inhibits dipeptidylpeptidase-IV activity 43) . In a rat model of type 2 diabetes, collagen peptides derived from the skin of Chum salmon were reported to protect carotid artery vascular endothelial cells by lowering blood glucose levels, and were found to decrease the expression of inflammatory cytokines and adipocytokines in the liver 44,45) . In addition, treatment with FCP has been shown to improve glucose and lipid metabolic profiles, insulin sensitivity, renal function, and hypertension management in patients with type 2 diabetes and hypertension, suggesting that FCP may have potential utility in patients with both type 2 diabetes and hypertension 41) . ...
Article
Fish collagen peptides (FCP) derived from the skin, bones and scales are commercially used as a functional food or dietary supplement for hypertension and diabetes. However, there is limited evidence on the effects of FCP on the osteoblast function in contrast to evidence of the effects on wound healing, diabetes and bone regeneration, which have been obtained from animal studies. In this narrative review, we expound on the availability of FCP by basic research using osteoblasts. Low-concentration FCP upregulates the expression of osteoblast proliferation, differentiation and collagen modifying enzyme-related genes. Furthermore, it could accelerate matrix mineralization. FCP may have potential utility as a biomaterial to improve collagen quality and promote mineralization through the mitogen-activated protein kinase and Smad cascades. However, there are few clinical studies on bone regeneration in human subjects. It is desirable to be applied clinically through clinical study as soon as possible, based on the results from basic research.
... Marine collagen peptides at a high concentration (4.5 g/kg/day) can increase insulin sensitivity in the diabetic rats by upregulating the expression of GLUT4 while decreasing the expression of inflammatory cytokines, oxidative stress biomarkers, and adipocytokines. Moreover, they enhance the glucose metabolism and insulin sensitivity [90]. ...
Article
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The growing smooth talk in the field of natural compounds is due to the ancient and current interest in herbal medicine and their potentially positive effects on health. Dozens of antidiabetic natural compounds were reported and tested in vivo, in silico, and in vitro. The role of these natural compounds, their actions on the insulin signaling pathway, and the stimulation of the glucose transporter-4 (GLUT4) insulin-responsive translocation to the plasma membrane (PM) are all crucial in the treatment of diabetes and insulin resistance. In this review, we collected and summarized a group of available in vivo and in vitro studies which targeted isolated phytochemicals with possible antidiabetic activity. Moreover, the in silico docking of natural compounds with some of the insulin signaling cascade key proteins is also summarized based on the current literature. In this review, hundreds of recent studies on pure natural compounds that alleviate type II diabetes mellitus (type II DM) were revised. We focused on natural compounds that could potentially regulate blood glucose and stimulate GLUT4 translocation through the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway. On attempt to point out potential new natural antidiabetic compounds, this review also focuses on natural ingredients that were shown to interact with proteins in the insulin signaling pathway in silico, regardless of their in vitro/in vivo antidiabetic activity. We invite interested researchers to test these compounds as potential novel type II DM drugs and explore their therapeutic mechanisms.
Chapter
Collagen is the most plentiful protein in mammals and considered the most significant part of the body structurally and functionally. The marine sponge is also an important and unexplored source for collagen productions until now. Among the biopolymers, collagen signifies one of the most utilized biomaterials in view of its superb biocompatibility, biodegradability, and low antigenicity, confirmed structure, and biologic features. The increasing enthusiasm for the utilization of marine collagen biomaterials and their important properties makes them useful for various biomedical applications. This chapter centers on the growing interest in marine collagen (MC)-based platforms for therapeutic applications. Specific consideration is given to the bioactive properties of MC that are being investigated in preclinical and clinical examinations. In this chapter, an analysis of the work reported on collagen derived from marine species and fish trashes is presented. This chapter also provides structure, extraction, sources, and various therapeutic applications about MC obtained from marine sources. The MC market is quickly examined to feature the area of interest and the most productive areas of interest. The present status and upcoming possibilities of marine collagen-based biomaterials are examined in general along with appropriate examples drawn from existing literature.
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Sulfated fucan/fucosylated chondroitin sulfate-dominated polysaccharide fraction from low-edible-value sea cucumber may be a good alternative to high-edible-value sea cucumber-derived polysaccharide for application in hypoglycemic functional foods. To evaluate the potential effect of low-edible-value sea cucumber-derived polysaccharide fraction on type 2 diabetes (T2DM), two sulfated fucan/fucosylated chondroitin sulfate-dominated polysaccharide fractions screening from 10 global commercial low-edible-value sea cucumber species were investigated to identify their anti-diabetics efficacies using a high-fat diet and streptozotocin-induced T2DM rat model. Sulfated fucan-dominated polysaccharide fraction from Thelenota ananas and fucosylated chondroitin sulfate-dominated polysaccharide fraction from Cucumaria frondosa ameliorated hyperglycemia, restored hypertriglyceridemia and hypercholesterolemia, decreased inflammatory status and oxidative stress, protected against liver injury, as well as improved insulin resistance and promoted accumulation of hepatic glycogen by activating IRS/PI3K/AKT signaling and regulating GSK-3β gene expression in T2DM rats. The current findings provide an available strategy for the commercialization of sea cucumber polysaccharide based-hypoglycemic functional food.
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Nutrition and dietary supplements have been used to promote a youthful appearance for millennia. Despite high public demand for these products, evidence supporting their efficacy is limited and often inconsistent. We discuss the structural and functional changes that occur in the skin during the aging process. We also review evidence supporting the use of nutritional supplements commonly used to promote a youthful appearance, including vitamins A, C, D, and E, essential fatty acids, coenzyme Q, collagen peptides, curcumin, polyphenols, flavonoids, probiotics, and silymarin. We also consider the role of advanced glycosylated end products, anti-inflammatory diets, and caloric restriction in delaying premature skin aging. While evidence supporting the use of some dietary interventions is promising, further long-term studies in humans are required to fully understand their effects on the promotion of a youthful appearance.
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Milk and fish are two important nutrient rich foods that have shown to possess positive effects in the management of type 2 diabetes mellitus (T2DM). Recent evidence from several interventional studies in humans have demonstrated the beneficial effects of bioactive proteins, peptides, and fatty acids derived from fish and milk sources in the prevention and management of T2DM. The anti-diabetic compounds present in the fish are proteins, peptides, and ω-3 polyunsaturated fatty acids (PUFA), while milk bioactive compounds are casein, casein derived peptides, whey proteins, and whey protein derived peptides. Fish and milk derived bioactive proteins, peptides and fatty acids exhibited anti-diabetic effects through several mechanisms. This review mainly focuses on the recent studies related to the anti-diabetic activities of fish and milk derived bioactive compounds (proteins, peptides, fatty acids) in humans, animals and in vitro, and mechanisms of action of these bioactive compounds in the management of T2DM.
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Collagen is a kind of biocompatible protein material, which is widely used in medical tissue engineering, drug delivery, cosmetics, food and other fields. Because of its wide source, low extraction cost and good physical and chemical properties, it has attracted the attention of many researchers in recent years. However, the application of collagen derived from terrestrial organisms is limited due to the existence of diseases, religious beliefs and other problems. Therefore, exploring a wider range of sources of collagen has become one of the main topics for researchers. Marine-derived collagen (MDC) stands out because it comes from a variety of sources and avoids issues such as religion. On the one hand, this paper summarized the sources, extraction methods and characteristics of MDC, and on the other hand, it summarized the application of MDC in the above fields. And on the basis of the review, we found that MDC can not only be extracted from marine organisms, but also from the wastes of some marine organisms, such as fish scales. This makes further use of seafood resources and increases the application prospect of MDC.
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The definition of metabolic syndrome (MetS) fairly varies from one to another guideline and health organization. Per description of world health organization, occurrence of hyperinsulinemia or hyperglycemia in addition to two or more factors of dyslipidemia, hypoalphalipoproteinemia, hypertension and or large waist circumference factors would be defined as MetS. Conventional therapies and drugs, commonly with adverse effects, are used to treat these conditions and diseases. Nonetheless, in the recent decades scientific community has focused on the discovery of natural compounds to diminish the side effects of these medications. Among many available bioactives, biologically active peptides have notable beneficial effects on the management of diabetes, obesity, hypercholesterolemia, and hypertension. Marine inclusive of fish peptides have exerted significant bioactivities in different experimental in-vitro, in-vivo and clinical settings. This review exclusively focuses on studies from the recent decade investigating hypoglycemic, hypolipidemic, hypercholesterolemic and anti-obesogenic fish and fish peptides. Related extraction, isolation, and purification methodologies of anti-MetS fish biopeptides are reviewed herein for comparison purposes only. Moreover, performance of biopeptides in simulated gastrointestinal environment and structure-activity relationship along with absorption, distribution, metabolism, and excretion properties of selected oligopeptides have been discussed, in brief, to broaden the knowledge of readers on the design and discovery trends of anti-MetS compounds.
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Collagen peptide from Acaudina molpadioides (AMP) showed antioxidative activity in H2O2‐induced RAW264.7 cells in our pervious study. In this study, it was observed that AMP could effectively improve the morphology and function of liver in CCl4‐induced mice. After 200 mg/kg AMP treatment, the content of MDA in liver decreased by 62.3%, and the level of antioxidant enzymes (SOD, GSH‐Px, and CAT) increased by more than 65%. Western blot results disclosed that AMP (200 mg/kg) upregulated the Nrf2 level by 73.8% and downregulated Keap1 by 41.0% in CCl4‐induced mice liver. The levels of p‐ERK, p‐JNK, and p‐p38 in 200 mg/kg AMP treatment groups decreased by 57.3%, 40.9%, and 40.6%, but the levels of p‐PI3K and p‐AKT increased by 162.6% and 60.3%, respectively. Furthermore, the trends of Nrf2, Keap1, p‐ERK, p‐JNK, p‐p38, p‐PI3K, and p‐AKT levels in H2O2‐induced RAW264.7 cells after AMP treatment were similar to the results in CCl4‐induced mice liver. These findings provided evidence that AMP exerted antioxidant activity via Keap1/Nrf2‐ARE, PI3K/AKT, and MAPKs pathways in vivo and in vitro. Therefore, the collagen peptide from A. molpadioides might represent a novel functional food to prevent acute liver injury via attenuation of oxidative stress.
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Diabetes mellitus (DM), a chronic metabolic disease, severely affects patients’ life and intensively increases risks of developing other diseases. It is estimated that 0.4 billion individuals worldwide are subjected to diabetes, especially type 2 diabetes mellitus. At present, although various synthetic drugs for diabetes such as Alogliptin and Rosiglitazone, etc. have been used to manage diabetes, some of them showed severe side effects. Given that the pathogenesis of type 2 diabetes mellitus, natural occurring drugs are beneficial alternatives for diabetes therapy with low adverse effects or toxicity. Recently, more and more plant-derived extracts or compounds were evaluated to have anti-diabetic activities. Their anti-diabetic mechanisms involve certain key targets like α-glucosidase, α-amylase, DPP-4, PPAR γ PTP1B, and GLUT4, etc. Here, we summarize the newly found anti-diabetic (type 2 diabetes mellitus) natural compounds and extracts from 2011-2017, and give the identification of their molecular targets. This review could provide references for the research of natural agents curing type 2 diabetes mellitus (T2DM).
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Background and aims Controlling glycemic levels is crucial for patients with diabetes mellitus to improve their disease management and health outcomes. Beyond lifestyle modification and pharmacotherapy, some supplements have been shown to lower blood glucose as well as mitigate diabetic complications. Methods Information was primarily gathered by employing various PubMed scholarly articles for real-world examples in addition to data extraction from supplementary manuscripts. Only original human trials were used, and those published within the past two decades were primarily chosen. However, background information may contains review articles. Results Some non-herbal supplements have been suggested to lower fasting blood glucose, postprandial glucose, glycated glucose (HbA1c), lipid profiles, oxidative stress, and inflammation, as well as improving body composition, insulin sensitivity, blood pressure, and nephropathy. Conclusion This review discusses ten non-herbal supplements that have been reported to have beneficial effects among different types of patients with diabetes as well as potiential future clinical application. However, more long-term studies with a larger amount and more diverse participants need to be conducted for a robust conclusion. Also, mechanisms of action of antidiabetic effects are poorly understood and need further research.
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Objective . To discuss the link between glycogen synthase kinase-3 (GSK3) and the main biological alterations demonstrated in bipolar disorder (BD), with special attention to the redox status and the evidence supporting the efficacy of lithium (a GSK3 inhibitor) in the treatment of BD. Methods . A literature research on the discussed topics, using Pubmed and Google Scholar, has been conducted. Moreover, a manual selection of interesting references from the identified articles has been performed. Results . The main biological alterations of BD, pertaining to inflammation, oxidative stress, membrane ion channels, and circadian system, seem to be intertwined. The dysfunction of the GSK3 signalling pathway is involved in all the aforementioned “biological causes” of BD. In a complex scenario, it can be seen as the common denominator linking them all. Lithium inhibition of GSK3 could, at least in part, explain its positive effect on these biological dysfunctions and its superiority in terms of clinical efficacy. Conclusions . Deepening the knowledge on the molecular bases of BD is fundamental to identifying the biochemical pathways that must be targeted in order to provide patients with increasingly effective therapeutic tools against an invalidating disorder such as BD.
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Objective To determine the effects and potential synergy of resistance training (RT), Huang Qi (HQ) herbal supplementation, and electroacupuncture (EA) on skeletal muscle mass, contractile properties, and components of the insulin signalling pathway in healthy Sprague Dawley rats. Methods Female Sprague Dawley rats were randomly assigned to one of five groups (n=8 each): control (CON), RT only, RT with EA (RT-EA), RT with HQ (RT-HQ), and RT combined with both EA and HQ (RT-EA-HQ). RT was performed using ladder climbing every other day for 8 weeks. Sparse-wave EA was applied for 15 min/day, 3 times/week for 8 weeks. HQ supplementation was provided via oral gavage daily for 8 weeks. Results RT significantly increased the muscle mass of the flexor hallucis longus (FHL) compared to CON. The isometric twitch and tetanic tension of the FHL in the RT-EA, RT-HQ, and RT-EA-HQ groups were significantly higher compared to CON and RT groups. RT-EA treatment (with or without HQ) significantly increased GLUT4 protein concentration but had no impact on Akt-2. Conclusions EA appears to be an effective treatment modality for increasing muscle mass and function when combined with RT. RT-EA may also be an effective method for improving glucose tolerance as a result of increases in GLUT4 protein concentration.
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Adipose tissue (AT) regulates systemic insulin sensitivity through multiple mechanisms, and alterations in de novo lipogenesis appear to contribute. Mice overexpressing GLUT4 in adipocytes (AG4OX) have elevated AT lipogenesis and enhanced glucose tolerance despite being obese and having elevated circulating fatty acids. Lipidomic analysis of AT identified a structurally unique class of lipids, branched fatty acid esters of hydroxy-fatty acids (FAHFAs), which were elevated in AT and serum of AG4OX mice. Palmitic acid esters of hydroxy-stearic acids (PAHSAs) are among the most upregulated FAHFA families in AG4OX mice. Eight PAHSA isomers are present in mouse and human tissues. PAHSA levels are reduced in insulin resistant people, and levels correlate highly with insulin sensitivity. PAHSAs have beneficial metabolic effects. Treatment of obese mice with PAHSAs lowers glycemia and improves glucose tolerance while stimulating glucagon-like peptide 1 and insulin secretion. PAHSAs also reduce inflammatory cytokine production from immune cells and ameliorate adipose inflammation in obesity. PAHSA isomer concentrations are altered in physiological and pathophysiological conditions in a tissue- and isomer-specific manner. The mechanisms most likely involve changes in PAHSA biosynthesis, degradation, and secretion. The discovery of PAHSAs reveals the existence of previously unknown endogenous lipids and biochemical pathways involved in metabolism and inflammation, two fundamental physiological processes.
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Recently, development and research of nutraceuticals based on marine collagen peptides (MCPs) have been growing due to their high homology with human collagens, safety, bioavailability through gut, and numerous bioactivities. The major concern regarding safety of MCPs intake relates to increased risk of oxidative stress connected with collagen synthesis (likewise in fibrosis) and to ROS production by MCPs-stimulated phagocytes. In this clinical-laboratory study, fish skin MCPs combined with plant-derived skin-targeting antioxidants (AO) (coenzyme Q 10 + grape-skin extract + luteolin + selenium) were administered to volunteers ( n = 41 ). Skin properties (moisture, elasticity, sebum production, and biological age) and ultrasonic markers (epidermal/dermal thickness and acoustic density) were measured thrice (2 months before treatment and before and after cessation of 2-month oral intake). The supplementation remarkably improved skin elasticity, sebum production, and dermal ultrasonic markers. Metabolic data showed significant increase of plasma hydroxyproline and ATP storage in erythrocytes. Redox parameters, GSH/coenzyme Q 10 content, and GPx/GST activities were unchanged, while NO and MDA were moderately increased within, however, normal range of values. Conclusions . A combination of MCPs with skin-targeting AOs could be effective and safe supplement to improve skin properties without risk of oxidative damage.
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We aim to investigate the association between elevated tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and high sensitivity-C-reactive protein (hs-CRP) with type 2 diabetes mellitus (T2DM) in abdominal obesity (AO) women subjects. A total of 428 AO subjects (age 48.4 ± 10.2 years), and 107 non-AO women subjects (age 48.8 ± 11.8 years) were enrolled for the all biochemistry testing, inflammatory cytokines, fasting insulin and Homeostasis Model Assessment of insulin resistance (HOMA-IR). Body mass index, waist circumference (WC), blood pressure (BP), plasma glucose (Glu), triglyceride (TG), insulin, HOMA-IR and inflammatory cytokines were significantly higher and lower total antioxidant capacity, HDL-C in AO subjects (p < 0.05). WC was significantly correlated with BP, Glu, TG, LDL-C, insulin, HOMA-IR, TNF-α, IL-6 and negative correlation with HDL-C in AO subjects. Elevation of TNF-α, IL-6, hs-CRP and insulin resistance were significantly associated with T2DM in AO subjects, after adjusting with insulin resistance, increased oxidative stress, elevated TG and reduced HDL-C by using multiple logistic regression analysis. In conclusions, elevation of inflammatory cytokines, oxidative stress and insulin resistance were associated with T2DM in AO women subjects. These inflammatory cytokines are positively associated with T2DM and may have a causal relation with an increased oxidative stress and insulin resistance in these AO women subjects.
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The goal of the present study was to investigate the wound-healing potential of marine collagen peptides (MCPs) from chum salmon skin administered to rats following cesarean section (CS). Ninety-six pregnant Sprague-Dawley rats were randomly divided into four groups: a vehicle group and three MCP groups. After CS, rats were intragastrically given MCPs at doses of 0, 0.13, 0.38, 1.15 g/kg*bw, respectively. On postoperative days 7, 14, and 21, the uterine bursting pressure, skin tensile strength, hydroxyproline (Hyp) concentrations, and histological and immunohistochemical characteristics of the scar tissue were examined. In the MCP groups, the skin tensile strength, uterine bursting pressure, and Hyp were significantly higher than those in the vehicle group at all three time points (p<0.05). The formation of capillary, fibroblast, and collagen fiber, the expression of platelet-endothelial cell adhesion molecule-1, basic fibroblast growth factor, and transforming growth factor beta-1 were increased in the MCP groups (p<0.05). MCPs could accelerate the process of wounding healing in rats after CS.
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insulin resistance, dyslipidemia, β-cell dysfunction, impaired glucose tolerance and ultimately leading to T2DM. Chronic oxidative stress, hyperglycemia and dyslipidemia are particularly dangerous for β-cells from lowest levels of antioxidant, have high oxidative energy requirements, decrease the gene expression of key β-cell genes and induce cell death. If β-cell functioning is impaired, it results in an under production of insulin, impairs glucose stimulated insulin secretion, fasting hyperglycemia and eventually the development of T2DM. Core tip: Oxidative stress is underling in the development of cardiovascular disease, type 2 diabetes mellitus (T2DM) and diabetic complications. Increased oxidative stress appears to be a deleterious factor leading to insulin resistance, dyslipidemia, β-cell dysfunction, impaired glucose tolerance and ultimately leading to T2DM. Tangvarasittichai S. Oxidative stress, insulin resistance, dyslipidemia and type 2 diabetes mellitus. World J Diabetes 2015; 6(3): 456-480 Available from:
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Marine bioresources are a valuable source of bioactive compounds with industrial and nutraceutical potential. Numerous clinical trials evaluating novel chemotherapeutic agents derived from marine sources have revealed novel mechanisms of action. Recently, marine-derived bioactive peptides have attracted attention owing to their numerous beneficial effects. Moreover, several studies have reported that marine peptides exhibit various anti-infective activities, such as antimicrobial, antifungal, antimalarial, antiprotozoal, anti-tuberculosis, and antiviral activities. In the last several decades, studies of marine plants, animals, and microbes have revealed tremendous number of structurally diverse and bioactive secondary metabolites. However, the treatments available for many infectious diseases caused by bacteria, fungi, and viruses are limited. Thus, the identification of novel antimicrobial peptides should be continued, and all possible strategies should be explored. In this review, we will present the structures and anti-infective activity of peptides isolated from marine sources (sponges, algae, bacteria, fungi and fish) from 2006 to the present.
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The present review describes research on novel natural antitumor alkaloids isolated from marine invertebrates. The structure, origin, and confirmed cytotoxic activity of more than 130 novel alkaloids belonging to several structural families (indoles, pyrroles, pyrazines, quinolines, and pyridoacridines), together with some of their synthetic analogs, are illustrated. Recent discoveries concerning the current state of the potential and/or development of some of them as new drugs, as well as the current knowledge regarding their modes of action, are also summarized. A special emphasis is given to the role of marine invertebrate alkaloids as an important source of leads for anticancer drug discovery.
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Peroxisome proliferator-activated receptors are expressed in many tissues, including adipocytes, hepatocytes, muscles and endothelial cells; however, the affinity depends on the isoform of PPAR, and different distribution and expression profiles, which ultimately lead to different clinical outcomes. Because they play an important role in lipid and glucose homeostasis, they are called lipid and insulin sensors. Their actions are limited to specific tissue types and thus, reveal a characteristic influence on target cells. PPARalpha mainly influences fatty acid metabolism and its activation lowers lipid levels, while PPARgamma is mostly involved in the regulation of the adipogenesis, energy balance, and lipid biosynthesis. PPARbeta/delta participates in fatty acid oxidation, mostly in skeletal and cardiac muscles, but it also regulates blood glucose and cholesterol levels. Many natural and synthetic ligands influence the expression of these receptors. Synthetic ligands are widely used in the treatment of dyslipidemia (e.g. fibrates - PPARalpha activators) or in diabetes mellitus (e.g. thiazolidinediones - PPARgamma agonists). New generation drugs - PPARalpha/gamma dual agonists - reveal hypolipemic, hypotensive, antiatherogenic, anti-inflammatory and anticoagulant action while the overexpression of PPARbeta/delta prevents the development of obesity and reduces lipid accumulation in cardiac cells, even during a high-fat diet. Precise data on the expression and function of natural PPAR agonists on glucose and lipid metabolism are still missing, mostly because the same ligand influences several receptors and a number of reports have provided conflicting results. To date, we know that PPARs have the capability to accommodate and bind a variety of natural and synthetic lipophilic acids, such as essential fatty acids, eicosanoids, phytanic acid and palmitoylethanolamide. A current understanding of the effects of PPARs, their molecular mechanisms and the role of these receptors in nutrition and therapeutic treatment are delineated in this paper.
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Resistin is an adipocyte- and monocyte-derived cytokine which has been implicated in the modulation of insulin action, energy, glucose and lipid homeostasis. Resistin has been associated with insulin resistance and many of its known complications. As a molecular link between metabolic signals, inflammation, and vascular dysfunction, resistin can be proposed as playing a significant role in the heightened inflammatory state induced by metabolic stress linked to excessive caloric intake, thus contributing to the risk for metabolic syndrome (MetS), type 2 diabetes (T2DM), and cardiovascular disease (CVD). In this review, we highlighted the role of resistin, as an inflammatory cytokine, in the development of CVD, T2DM and the MetS.
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Due to the increased consumption of marine collagen peptides preparation (MCP) as ingredients in functional foods and pharmaceuticals, it was necessary to carry out safety requirements in the form of an oral chronic toxicity assessment. In order to define the oral chronic toxicity of MCP, a 24-month feeding study of MCP was carried out. Sprague-Dawley (S-D) rats at the age of four-week of both sexes were treated with MCP at the diet concentrations of 0%, 2.25%, 4.5%, 9% and 18% (wt/wt). The actual food intake and bodyweight of the individual animals were recorded periodically until sacrifice. Blood and urine samples were collected for serum chemistry evaluations and urinalysis. Throughout the experimental period, there was no toxicologically significant difference between the vehicle and MCP-treated animals with respect to the survival rate, body weight, food consumption, urinalysis, clinical biochemistry parameter and relative organ weight in either sex. Moreover, incidences of non-neoplastic lesions in MCP-treated groups did not significantly increase compared with the control group. Under the present experimental conditions, no higher risk of chronic toxic effects was observed in MCP-treated rats at the diet concentrations of 2.25%, 4.5%, 9% and 18% (wt/wt) than in the rats fed with basal rodent diet.
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Adipocyte-derived secretory proteins have been increasingly linked to diabetes. To investigate whether adiponectin, a major adipocyte secretory protein, predicts diabetes, we conducted a case-cohort study representing the approximately 9-year experience of the 10,275 middle-aged, U.S. African-American and white participants of the Atherosclerosis Risk in Communities (ARIC) study. Adiponectin was measured on stored plasma of 581 incident diabetes case subjects and 572 noncase subjects. Overall hazard ratios (95% CIs) for developing diabetes, for those in the second, third, and fourth (versus the first) quartile of adiponectin were 0.57 (0.41-0.78), 0.39 (0.27-0.56), and 0.18 (0.11-0.27), respectively, after adjustment for age, sex, ethnicity, study center, parental history of diabetes, and hypertension and 0.72 (0.48-1.09), 0.67 (0.43-1.04), and 0.58 (0.34-0.99), respectively, after additional adjustment for BMI, waist-to-hip ratio, fasting glucose, insulin, and a score composed of six inflammation markers. The association was of similar magnitude in men and women and in whites and African Americans, but was absent in smokers and in those with a greater inflammation score (interaction P < 0.01 for each). In conclusion, in this community-based sample of U.S. adults, higher adiponectin levels were associated with a lower incidence of diabetes.
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The objective of the present study was to develop a rat model that replicates the natural history and metabolic characteristics of human type 2 diabetes and is also suitable for pharmacological screening. Male Sprague-Dawley rats (160-180 g) were divided into two groups and fed with commercially available normal pellet diet (NPD) (12% calories as fat) or in-house prepared high-fat diet (HFD) (58% calories as fat), respectively, for a period of 2 weeks. The HFD-fed rats exhibited significant increase in body weight, basal plasma glucose (PGL), insulin (PI), triglycerides (PTG) and total cholesterol (PTC) levels as compared to NPD-fed control rats. Besides, the HFD rats showed significant reduction in glucose disappearance rate (K-value) on intravenous insulin glucose tolerance test (IVIGTT). Hyperinsulinemia together with reduced glucose disappearance rate (K-value) suggested that the feeding of HFD-induced insulin resistance in rats. After 2 weeks of dietary manipulation, a subset of the rats from both groups was injected intraperitoneally with low dose of streptozotocin (STZ) (35 mg kg(-1)). Insulin-resistant HFD-fed rats developed frank hyperglycemia upon STZ injection that, however, caused only mild elevation in PGL in NPD-fed rats. Though there was significant reduction in PI level after STZ injection in HFD rats, the reduction observed was only to a level that was comparable with NPD-fed control rats. In addition, the levels of PTG and PTC were further accentuated after STZ treatment in HFD-fed rats. In contrast, STZ (35 mg kg(-1), i.p.) failed to significantly alter PI, PTG and PTC levels in NPD-fed rats. Thus, these fat-fed/STZ-treated rats simulate natural disease progression and metabolic characteristics typical of individuals at increased risk of developing type 2 diabetes because of insulin resistance and obesity. Further, the fat-fed/STZ-treated rats were found to be sensitive for glucose lowering effects of insulin sensitizing (pioglitazone) as well as insulinotropic (glipizide) agents. Besides, the effect of pioglitazone and glipizide on the plasma lipid parameters (PTG and PTC) was shown in these diabetic rats. The present study represents that the combination of HFD-fed and low-dose STZ-treated rat serves as an alternative animal model for type 2 diabetes simulating the human syndrome that is also suitable for testing anti-diabetic agents for the treatment of type 2 diabetes.
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Type 2 diabetes is a worldwide increasing disease resulting from the interaction between a subject's genetic makeup and lifestyle. In genetically predisposed subjects, the combination of excess caloric intake and reduced physical activity induces a state of insulin resistance. When beta cells are no longer able to compensate for insulin resistance by adequately increasing insulin production, impaired glucose tolerance appears, characterized by excessive postprandial hyperglycemia. Impaired glucose tolerance may evolve into overt diabetes. These 3 conditions, ie, insulin resistance, impaired glucose tolerance, and overt diabetes, are associated with an increased risk of cardiovascular disease. Because all these conditions are also accompanied by the presence of an oxidative stress, this article proposes oxidative stress as the pathogenic mechanism linking insulin resistance with dysfunction of both beta cells and endothelium, eventually leading to overt diabetes and cardiovascular disease. This hypothesis, moreover, may also contribute to explaining why treating cardiovascular risk with drugs, such as calcium channel blockers, ACE inhibitors, AT-1 receptor antagonists, and statins, all compounds showing intracellular preventive antioxidant activity, results in the onset of new cases of diabetes possibly being reduced.
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Adipose tissue regulates numerous physiological processes, and its dysfunction in obese humans is associated with disrupted metabolic homeostasis, insulin resistance and type 2 diabetes mellitus (T2DM). Although several US-approved treatments for obesity and T2DM exist, these are limited by adverse effects and a lack of effective long-term glucose control. In this Review, we provide an overview of the role of adipose tissue in metabolic homeostasis and assess emerging novel therapeutic strategies targeting adipose tissue, including adipokine-based strategies, promotion of white adipose tissue beiging as well as reduction of inflammation and fibrosis.
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The present study was performed to evaluate the insulin-like effects of zinc in normal L6 myotubes as well as its ability to alleviate insulin resistance. Glucose consumption was measured in both normal and insulin-resistant L6 myotubes. Western blotting and immunofluorescence revealed that zinc exhibited insulin-like glucose transporting effects by activating key markers that are involved in the insulin signaling cascade (including Akt, GLUT4, and GSK3β), and downregulating members of the insulin signaling feedback cascade such as mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase (S6 K1). In normal L6 myotubes zinc enhanced glucose consumption via a mechanism that might involve the activation of Akt phosphorylation, glucose transporter 4 (GLUT4) translocation, and GSK3β phosphorylation. In contrast zinc exerted insulin-mimetic effects in insulin-resistant L6 myotubes by upregulating Akt phosphorylation, GLUT4 translocation, and GSK3β phosphorylation, and downregulating the expression of mTOR and S6 K1. In conclusion, zinc might enhance glucose consumption by modulating insulin signaling pathways including Akt-GLUT4, GSK3β, mTOR, and S6 K1.
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The year 2015 was punctuated by numerous events in diabetology. First, the ADA/EASD guidelines have been updated. The pharmacological panel for type 2 diabetes treatment saw the arrival of different new molecules. Two new basal insulins were also approved. Also, cardiovascular safety trials have been published regarding recent antidiabetic drugs. A new insulin pump than can be coupled with a glucosensor was released. Finally, a new unexpected complication of SGLT2 inhibitors treatment was reported, the euglycemic keto-acidosis.
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In this study, we first report characterization of collagencin, an antimicrobial peptide identified from fish collagen hydrolysate. The peptide completely inhibited the growth of Staphylococcus aureus at 1.88 mM. Although non-toxic up to 470 μM, collagencin was hemolytic at higher concentrations. The secondary structure of collagencin was mainly composed by β-sheet and β-turn as determined by CD measurements and molecular dynamics. The peptide is likely to form β-sheet structure under hydrophobic environments and interacts with both anionic (phosphatidylglycerol) and zwitterionic (phosphoethanolamine and phosphatidylcholine) lipids as shown with CD spectroscopy and molecular dynamics. The peptide formed several hydrogen bonds with both POPG and POPE lipids and remained at membrane–water interface, suggesting that collagencin antibacterial action follows a carpet mechanism. Collagenous fish wastes could be processed by enzymatic hydrolysis and transformed into products of high value having functional or biological properties. Marine collagens are a promising source of antimicrobial peptides with new implications in food safety and human health.
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Background: Marine collagen peptide is a kind of oligopeptide powder at the relative molecular mass of less than 1 000, comprising 2-6 amino acids. Its antioxidation property has been proved in vitro. Objective: To study the effect of marine collagen peptide on the expression of overoxidation stress markers in the blood serum of rats with type 2 diabetes. Design, time and setting: A randomized control animal study was carried out from October 2006 to June 2007 at the Laboratory of Animal Experiment in Shenzhen Center for Disease Control and Prevention (Shenzhen, Guangdong, China). Materials: Marine collagen peptide was offered by the China National Research Institute of Food and Fermentation Industry. Thirty-six male SD rats were assigned into 6 controls and 30 models. Normal control group fed with basal diet, while 26 of other 30 rats were successfully induced the model of type 2 diabetes by intraperitoneal injection of streptozotocin. Methods: Twenty-four rats with type 2 diabetes were randomly divided into four groups, namely marine collagen peptide low dose group (0.75 g/ kg ·d), medium dose group (1.5 g/kg ·d), high dose group (3.0 g/kg ·d) and diabetes control group. They were all processed into intragastric administration of tap water for 4 weeks. Main outcome measures: Blood glucose of rats before intervention and at four weeks after intervention. Blood level of superoxide dismutase (SOD), malondialdehyde (MDA), reduced glutathione hormone (GSH) and NO of rats at four weeks after intervention. Results: There were no significant differences among three marine collagen peptide groups on the blood glucose (P > 0.05). Compared to normal control group, the levels of SOD and GSH of all groups were significantly lowered, while the levels of MDA and NO were significantly enhanced (P < 0.01, 0.05); Compared to the diabetes control group, the SOD and GSH levels of marine collagen peptide middle and high dose groups were significantly increased, while the MDA and NO levels were significantly lowered (P < 0.01, 0.05). Conclusion: Higher dosage of marine collagen peptide (≥ 1.5 g/kg ·d) may have a regulating effect on the expression of overoxidation markers in rats with type 2 diabetes. The exact effect of marine collagen peptide on fasting blood glucose deserves further study of large scale samples and intervention time.
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Decreased GLUT4 expression and impaired GLUT4 cell membrane translocation are involved in type 2 diabetes mellitus (T2DM) pathogenesis so the factors impacting GLUT4 expression may be associated with T2DM. In this study, we identified four miRNAs: miR-31, miR-93, miR-146a, and miR-199a which suppress GLUT4 expression in HEK293T cells. Subsequently, we determined expression of these four miRNAs in plasma samples of T2DM patients, T2DM susceptible individuals, and healthy controls and found miR-199a was overexpressed in patients' plasma compared with healthy control. Because the miR-199a binding site in GLUT4 3'UTR is highly conserved among vertebrates, we detected the glucose uptake in rat L6 myoblast cells through gain- and loss-of-function of miR-199a. We found that miR-199a can repress glucose uptake in L6 cells, which was rescued by GLUT4 overexpression. These results indicate that T2DM patients may have a high level miR-199a that reduce GLUT4 expression and contribute to the insulin resistance. Hence, miR-199a may be a novel biomarker for risk estimation and classification in T2DM patients.
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The present study aimed to evaluate the effect of an oral administration of marine collagen peptides (MCPs) pre- and post-acute ethanol intoxication in female Sprague-Dawley (SD) rats. MCPs were orally administered to rats at doses of 0 g per kg bw, 2.25 g per kg bw, 4.5 g per kg bw and 9.0 g per kg bw, prior to or after the oral administration of ethanol. Thirty minutes after ethanol treatment, the effect of MCPs on motor incoordination and hypnosis induced by ethanol were investigated using a screen test, fixed speed rotarod test (5 g per kg bw ethanol) and loss of righting reflex (7 g per kg bw ethanol). In addition, the blood ethanol concentrations at 30, 60, 90, and 120 minutes after ethanol administration (5 g per kg bw ethanol) were measured. The results of the screen test and fixed speed rotarod test suggested that treatment with MCPs at 4.5 g per kg bw and 9.0 g per kg bw prior to ethanol could attenuate ethanol-induced loss of motor coordination. Moreover, MCP administered both pre- and post-ethanol treatment had significant potency to alleviate the acute ethanol induced hypnotic states in the loss of righting reflex test. At 30, 60, 90 and 120 minutes after ethanol ingestion at 5 g per kg bw, the blood ethanol concentration (BEC) of control rats significantly increased compared with that in the 4.5 g per kg bw and 9.0 g per kg bw MCP pre-treated groups. However, post-treatment with MCPs did not exert a significant inhibitory effect on the BEC of the post-treated groups until 120 minutes after ethanol administration. Therefore, the anti-inebriation effect of MCPs was verified in SD rats with the possible mechanisms related to inhibiting ethanol absorption and facilitating ethanol metabolism. Moreover, the efficiency was better when MCPs were administered prior to ethanol.
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Obesity, especially of the abdominal type, is a health problem that constitutes metabolic syndrome and increases the incidence of various diseases, including diabetes, hypertension, dyslipidemia, atherosclerosis, and cancer. Various mechanisms linking obesity to these associated diseases have been postulated. One candidate is oxidative stress, which has been implicated in vascular complications of diabetes and in pancreatic -cell failure in diabetes. Notably, obese people without diabetes also display elevated levels of systemic oxidative stress. In addition, levels of oxidative stress are increased in the adipose tissue in obese mice. Treating obese mice with antioxidant agents attenuates the development of diabetes. In 3T3-L1 adipocytes, increases in reactive oxygen species (ROS) occur with lipid accumulation; the addition of free fatty acids elevates ROS generation further. Thus, adipose tissue represents an important source of ROS; ROS may contribute to the development of obesity-associated insulin resistance and type 2 diabetes. Moreover, the levels of oxidative stress present in several other types of cells or tis-sues, including those in the brain, arterial walls, and tumors, have been implicated in the pathogenesis associated with hypertension, atherosclerosis, and cancer. The increased levels of systemic oxidative stress that occur in obesity may contribute to the obesity-associated development of these diseases.
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Insulin resistance is defined as situation where there is insufficient biological or metabolic response to normal plasma levels of insulin. For precise quantification of insulin sensitivity, the euglycemic hyperinsulinemic clamp may be used, but it is expensive, invasive and used mainly in research settings. HOMA-IR (Homeostasis Model Assessment-Insulin Resistance) and ISI 0,120 (Insulin Sensitivity Index) are indirect markers of insulin resistance. The present study evaluated the usefulness of the surrogate markers for evaluation of Insulin resistance in clinical settings. This study was carried out on 120 subjects. Of these, 60 subjects presenting with two or more features of metabolic syndrome (Hypertension, Obesity, Dyslipidemia, altered glucose tolerance) were included in the study group. Sixty age and sex matched healthy controls were selected with normal Body mass index. All the subjects underwent a standard Oral Glucose Tolerance Test. Plasma glucose and serum insulin were estimated using Glucose oxidase and ELISA principle respectively. HOMA-IR and ISI 0,120 were calculated using relevant formulae. The HOMA-IR values were significantly raised in suspected Insulin resistant subjects (6.74±1.24) as compared to healthy controls (0.82±0.017) (p=0.001). ISI 01,20 was significantly low in insulin resistant subjects (3.13±0.17) as compared to controls (20.60±0.37) (p<0.001). Insulin sensitivity index showed a significant negative correlation with HOMA-IR. A significant negative correlation was observed between serum cholesterol, serum LDL-cholesterol and ISI 0,120 indicating that dyslipidemia in metabolic syndrome may result from a decrease in Insulin sensitivity. HOMA-IR and ISI 0,120 are simple, convenient and sensitive estimates of insulin resistance adaptable for use in clinical practice as well as large-scale epidemiological studies.
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To observe the neuroprotective effects of marine collagen peptide (MCP) isolated from Chum Salmon (Oncorhynchus keta) skin by enzymatic hydrolysis, 20-month-old female C57BL/6J mice were fed with chow diet, 0.22%, 0.44% or 1.32% (wt/wt) MCP diet for 3 months. Comparing with aged control group, the abilities of passive avoidance and spatial memory and learning were significantly enhanced evaluated by step-down test and Morris water maze respectively. Furthermore, the abilities of learning and memory had no significant difference between 0.44% and 1.32% MCP treated groups and young control group. The alleviated oxidative stress, reduced apoptotic neurons, up-regulated expression of brain-derived neurotrophic factor (BDNF) and postsynaptic density protein 95 (PSD95) were observed in MCP treated groups compared with aged control group. Our research revealed that there were no significant difference between 0.44% and 1.32% MCP treated groups and young control group. These findings suggest that MCP could be a candidate for functional food to relieve memory deficits associated with aging.
Article
Hypertension is the most widespread risk factor for many serious cardiovascular diseases. Angiotensin-converting enzyme (ACE) plays a crucial role in cardiovascular physiological regulation by converting angiotensin I to a potent vasoconstrictor, angiotensin II. Hence, the inhibition of ACE is a key target for antihypertensive activity. Recently, potent antihypertensive peptides have been purified widely by enzymatic hydrolysis of muscle protein, skin collagen, and gelatin of many different kinds of marine fishes. Marine fish-derived bioactive peptides can be developed as antihypertensive components in functional foods or nutraceuticals. This contribution presents an overview of the ACE inhibitory peptides derived from marine fishes and discusses their future prospects to be used as potential drug candidates for preventing and treating high blood pressure.
Article
The increasing prevalence, variable pathogenesis, progressive natural history, and complications of type 2 diabetes emphasise the urgent need for new treatment strategies. Longacting (eg, once weekly) agonists of the glucagon-like-peptide-1 receptor are advanced in development, and they improve prandial insulin secretion, reduce excess glucagon production, and promote satiety. Trials of inhibitors of dipeptidyl peptidase 4, which enhance the effect of endogenous incretin hormones, are also nearing completion. Novel approaches to glycaemic regulation include use of inhibitors of the sodium-glucose cotransporter 2, which increase renal glucose elimination, and inhibitors of 11β-hydroxysteroid dehydrogenase 1, which reduce the glucocorticoid effects in liver and fat. Insulin-releasing glucokinase activators and pancreatic-G-protein-coupled fatty-acid-receptor agonists, glucagon-receptor antagonists, and metabolic inhibitors of hepatic glucose output are being assessed. Early proof of principle has been shown for compounds that enhance and partly mimic insulin action and replicate some effects of bariatric surgery.
Article
Stroke is a leading cause of mortality and disability. Nicotinamide phosphoribosyltransferase (Nampt) is the rate-limiting enzyme in mammalian nicotinamide adenine dinucleotide (NAD)(+) biosynthesis and contributes to cell fate decisions. However, the role of Nampt in brain and stroke remains to be investigated. We used lentivirus-mediated Nampt overexpression and knockdown to manipulate Nampt expression and explore the effects of Nampt in neuronal survival on ischemic stress both in vivo and in vitro. We also used adenosine monophosphate (AMP)-activated kinase-α2 (AMPKα2) and silent mating type information regulation 2 homolog 1 (SIRT1) knockout mice to investigate the underlying mechanisms of Nampt neuroprotection. Nampt inhibition by a highly-specific Nampt inhibitor, FK866, aggravated brain infarction in experimentally cerebral ischemia rats, whereas Nampt overexpression in local brain and Nampt enzymatic product nicotinamide mononucleotide (NMN) reduced ischemia-induced cerebral injuries. Nampt overexpression and knockdown regulated neuron survival via the AMPK pathway. Neuroprotection of Nampt was abolished in AMPKα2(-/-) neurons. In neurons, Nampt positively modulated NAD(+) levels and thereby controlled SIRT1 activity. SIRT1 coprecipitated with serine/threonine kinase 11 (LKB1), an upstream kinase of AMPK, and promoted LKB1 deacetylation in neurons. Nampt-induced LKB1 deacetylation and AMPK activation disappeared in SIRT1(-/-) neurons. In contrast, Ca(2+) /calmodulin-dependent protein kinase kinase-β (CaMKK-β), another upstream kinase of AMPK, was not involved in the neuroprotection of Nampt. More important, Nampt overexpression-induced neuroprotection was abolished in SIRT1(+/-) and AMPKα2(-/-) mice. Our findings reveal that Nampt protects against ischemic stroke through rescuing neurons from death via the SIRT1-dependent AMPK pathway and indicate that Nampt is a new therapeutic target for stroke.
Article
This study was aimed at examining the therapeutic effects of marine collagen peptides (MCPs) from fish hydrolysate in Chinese patients with type 2 diabetes mellitus (T2DM). A total of 100 diabetic patients and 50 healthy controls were recruited. Diabetic patients were randomized into treatment and control groups. The patients in the treatment group received an additional 13 g of MCPs daily for 3 months. Their blood samples were collected before, and 1.5 and 3 months after, treatment to evaluate glucose and lipid metabolism. The levels of serum high-sensitivity C-reactive protein (hs-CRP), nitric oxide (NO), bradykinin, prostacyclin (PGI2), and adipokines were determined. Significantly reduced levels of fasting blood glucose, human glycated hemoglobin A1c (GHbA1c), fasting blood insulin, total triglycerides, total cholesterol, low-density lipoprotein, and free-fatty acids, but increased levels of insulin sensitivity index and HDL were observed in T2DM patients following treatment with MCPs for 1.5 and 3 months. The values of these measures were significantly lower or higher than those of patient controls (p < 0.01), respectively. Interestingly, significantly decreased levels of hs-CRP and NO, but increased levels of bradykinin, PGI2, and adiponectin were detected in MCP-treated T2DM patients (p < 0.01), as compared with their basal values or the levels in patient controls. MCP treatment improved glucose and lipid metabolism in diabetic patients.
Article
Marine collagen peptides (MCPs) from deep sea fish are shown to ameliorate hyperlipidemia in animal models. The study aimed at examining the effects of MCPs on glucose and lipid metabolism in Chinese patients with type 2 diabetes mellitus (T2DM) and primary hypertension. One hundred patients with T2DM and primary hypertension and 50 healthy subjects (normal controls) were recruited for a randomized double blind study. The patients were randomized into MCPs treatment or patient control groups (n = 50 per group). Both patient controls and normal controls were given carboxymethylcellulose twice daily whereas the MCPs treatment group was given MCPs twice daily for 3 months. Blood pressure, glucose and lipid metabolism, serum high-sensitivity C-reactive protein, cytochrome P450, nitric oxide, bradykinin, prostacyclin, creatinine, uric acid and adipokines were measured at baseline, 1.5 and 3 months after treatment. All patients received regular medicines for control of hyperglycemia and hypertension. Compared with patient controls, significantly reduced levels of fasting blood glucose, HbA1c, diastolic blood pressure, mean arterial pressure and creatinine but increased levels of Insulin Sensitivity Index and Insulin Secretion Index were observed in patients receiving MCPs treatment. Furthermore, significantly reduced levels of serum triglycerides, total cholesterol, low-density lipoprotein, free fatty acids, cytochrome P450, nitric oxide and prostacyclin but increased levels of high-density lipoprotein, bradykinin and adiponectin were detected in patients taking MCPs. MCPs supplement may benefit glucose and lipid metabolism, insulin sensitivity, renal function and hypertension management in Chinese patients with T2DM and hypertension.
Article
The global diabetes burden is predicted to rise to 380 million by 2025 and would present itself as a major health challenge. However, both Type 1 and Type 2 diabetes increase the risk of developing micro-vascular complications and macro-vascular complications which in turn will have a devastating impact on quality of life of the patients and challenge health services Worldwide. The micro-vascular complications that affect small blood vessels are the leading cause of blindness (diabetic retinopathy) in the people of the working-age, end-stage renal disease (diabetic nephropathy) the most common cause of kidney failure today, and foot amputation (diabetic neuropathy) in patients with Type 1 and Type 2 diabetes. It is accepted that hyperglycemia is a major causative factor for the development of these complications, there is also growing evidence for the role of inflammation. Here we discuss low-grade inflammation as a common retinal-renal-nerve pathogenic link in patients with Type 1 and Type 2 diabetes. This review summarizes evidence showing a link between circulating and locally produced inflammatory biomarkers, such as cell adhesion molecules (vascular adhesion cell molecule-1, VCAM-1; intracellular adhesion molecule-1, ICAM-1), pro-inflammatory cytokines (interleukin-6, IL-6; tumour necrosis factor-alpha, TNF-α; C-reactive protein, CRP) with the development and progression of diabetic micro-vascular complications.
Article
This study aimed at investigating whether treatment with oligopeptides from marine salmon skin (OMSS) could modulate type 2 diabetes mellitus (T2DM)-related hyperglycemia and β-cell apoptosis in rats induced by high fat diet and low doses of streptozotocin and its therapeutic mechanisms. Groups of T2DM rats were treated with OMSS or bovine serum albumin (3.0 g/kg/d) for 4 wk and their blood samples, together with those of normal control rats, were collected before and 4 wk after treatment. The levels of fasting blood glucose (FBG) and insulin, serum superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH), tumor necrosis factor-alpha (TNFα), and interferon-gamma (IFNγ) in rats were determined. The islet cell apoptosis and Fas/FasL expression were detected by TUNEL and immunohistochemistry. In comparison with control rats, higher levels of FBG and frequency of apoptotic islet cells were detected in the bovine serum albumin group of diabetic rats, accompanied by higher levels of Fas expression in the pancreatic islets, serum TNFα, IFNγ, and MDA, but lower levels of SOD and GSH. However, the levels of FBG and frequency of apoptotic islet cells were significantly reduced in OMSS-treated rats. Lower levels of Fas expression were observed in the pancreatic islets of OMSS-treated rats. Significantly reduced levels of serum TNFα, IFNγ, and MDA, but increased levels of SOD and GSH, were detected in OMSS-treated rats. Treatment with OMSS significantly reduced FBG in diabetic rats. This antidiabetic activity may be mediated by down-regulating T2DM-related oxidative stress and inflammation, protecting the pancreatic β-cells from apoptosis.
Article
To explore Effects of marine collagen peptides (MCPs) on markers of metablic nuclear receptors, i.e peroxisome proliferator-activated receptor (PPARs), liver X receptor (LXRs) and farnesoid X receptor (FXRs) in type 2 diabetic patients with/without hypertension. METHOD Study population consisted of 200 type 2 diabetic patients with/without hypertension and 50 healthy subjects, all of whom were randomly assigned to MCPs-treated diabetics (n = 50), placebo-treated diabetics (n = 50), MCPs-treated diabetics with hypertension (n=50), placebo-treated diabetics with hypertension (n = 50), and healthy controls (n = 50). MCPs or placebo (water-soluble starch) were given daily before breakfast and bedtime over three months. Levels of free fatty acid, cytochrome P450, leptin, resistin, adiponectin, bradykinin, NO, and Prostacyclin were determined before intervention, and 1.5 months, and 3 months after intervention. Hypoglycemia and the endpoint events during the study were recorded and compared among the study groups. At the end of the study period, MCPs-treated patients showed marked improvement compared with patients receiving placebo. The protection exerted by MCPs seemed more profound in diabetics than in diabetics with hypertension. In particular, after MCPs intervention, levels of free fatty acid, hs-CRP, resistin, Prostacyclin decreased significantly in diabetics and tended to decrease in diabetic and hypertensive patients whereas levels of cytochrome P450, leptin, NO tended to decrease in diabetics with/without hypertension. Meanwhile, levels of adiponectin and bradykinin rose markedly in diabetics following MCPs administration. MCPs could offer protection against diabetes and hypertension by affecting levels of molecules involved in diabetic and hypertensive pathogenesis. Regulation on metabolic nuclear receptors by MCPs may be the possible underlying mechanism for its observed effects in the study. Further study into its action may shed light on development of new drugs based on bioactive peptides from marine sources.
Article
To observe the effects of marine collagen peptides (MCPs) on blood glucose and lipid metabolism in hyperinsulinemic rats. Male SD rats fed with high fat diet for 4 months were used to establish a hyperinsulinemic model. Thirty two hyperinsulinemic rats were divided into four groups according to body weight and serum insulin level, namely hyperinsulinemic control (HIC) group and 3 Marine Collagen Peptides treated groups with 8 rats in each group. Another 8 healthy male SD rats fed with basic diet were used as negative control (NC). Rats in MCPs groups were treated by intragastric way with MCPs at the dose of 0.225 g/kg bw, 0.45 g/kg bw and 1.35 g/kg bw respectively for 8 weeks, while rats in HIC and NC groups were treated with tap water in the same manner. During the test period, rats in HIC and MCPs groups were fed with high fat diet sequentially, while rats in NC group were fed with basic diet. Fasting serum glucose (GLU), insulin (INS) and lipids were assayed respectively before and after MCPs treatment. Oral glucose tolerance test, antioxidase activity, serum malondialdehyde (MDA) levels and the ultrastructure of islet beta cell were carried out at the end of the experiment. After 8 weeks of treatment, compared with HIC group, fasting INS, TC and TG of all three MCPs-treated groups decreased obviously, while fasting GLU level lowered significantly in 0.225 g/kg bw and 1.35 g/kg bw MCPs groups. Moreover, GLU level at 0.5 h, 2 h and the area under blood sugar curve in OGTT were evidently lower in 0.45 g/kg bw and 1.35 g/kg bw MCPs groups. Besides, serum SOD activity increased in all MCPs groups, and serum GSH-Px activity elevated obviously in 1.35 g/kg bw MCPs group, while serum MDA reduced. Finally, the ultrastructural impairment of islet resulted from high fat diet was improved evidently by 1.35 g/kg bw MCPs. MCPs was effective in improving glucose and lipid metabolism in hyperinsulinemic rats induced by high fat diet.
Article
Vascular cell adhesion molecule-1 (VCAM-1), an inducible cell-cell recognition protein on the endothelial cell surface (EC), has been associated with early stages of atherosclerosis. In view of the accelerated vascular disease observed in patients with diabetes, and the enhanced expression of VCAM-1 in diabetic rabbits, we examined whether irreversible advanced glycation endproducts (AGEs), could mediate VCAM-1 expression by interacting with their endothelial cell receptor (receptor for AGE, RAGE). Exposure of cultured human ECs to AGEs induced expression of VCAM-1, increased adhesivity of the monolayer for Molt-4 cells, and was associated with increased levels of VCAM-1 transcripts. The inhibitory effect of anti-RAGE IgG, a truncated form of the receptor (soluble RAGE) or N-acetylcysteine on VCAM-1 expression indicated that AGE-RAGE-induced oxidant stress was central to VCAM-1 induction. Electrophoretic mobility shift assays on nuclear extracts from AGE-treated ECs showed induction of specific DNA binding activity for NF-kB in the VCAM-1 promoter, which was blocked by anti-RAGE IgG or N-acetylcysteine. Soluble VCAM-1 antigen was elevated in human diabetic plasma. These data are consistent with the hypothesis that AGE-RAGE interaction induces expression of VCAM-1 which can prime diabetic vasculature for enhanced interaction with circulating monocytes.
Article
Insulin was discovered more than 75 years ago, but only recently have we begun to understand the mechanisms by which insulin promotes the uptake of glucose into cells. This review discusses recent advances, their contribution to our understanding of the pathogenesis of diabetes mellitus, and their implications for the design of new therapies to prevent and treat diabetes and its complications. Role of Glucose Transporters in Maintaining Glucose Homeostasis Carbohydrates, and glucose in particular, are an important source of energy for most living organisms. Tissues such as the brain need glucose constantly, and low blood concentrations of glucose can cause . . .
Article
Reactive oxygen species (ROS), generated either extracellularly or intracellularly through ligand-receptor interactions, can function as signal transduction molecules to activate the chemotactic cytokine interleukin-8 (IL-8) and the cell surface adhesion protein, intercellular adhesion molecule-1 (ICAM-1; CD54). Together, IL-8 and ICAM-1 orchestrate the transendothelial migration of neutrophils to sites of inflammation and injury. Recent results demonstrate that oxidant stress generated directly by exogenous H2O2 differentially induce IL-8 and ICAM-1 transcription in epithelial and endothelial cells. H2O2 induces IL-8 but not ICAM-1 in the A549 type-II-like epithelial cell line, whereas in a microvessel endothelial cell line (HMEC-1) as well as in primary endothelial cells, H2O2 induces ICAM-1 but not IL-8, which is spontaneously expressed. In contrast, the pro-inflammatory cytokine TNFalpha, whose activity is dependent on the generation of intracellular ROS, induces IL-8 and ICAM-1 in both cell types. The differential induction of IL-8 and ICAM-1 by H2O2 and TNFalpha suggest that the two inflammatory stimuli target distinct redox responsive signaling pathways to activate cell type-specific gene expression. In this regard, we found that the cell type-specific pattern of IL-8 and ICAM-1 gene expression was associated with the differential activation and promoter binding of the redox regulated transcription factors AP-1 and NF-kappaB. In this review, our current understanding of the redox regulation of the IL-8 and ICAM-1 genes is summarized, and the differential roles AP-1 and NF-kappaB play in their cell type-specific expression, with particular emphasis on the differential effects induced by TNFalpha and H2O2 is discussed.
Article
Numerous studies across several population groups have indicated that insulin resistance plays a central role in the development of type 2 diabetes mellitus (T2DM). Moreover, this disorder is also strongly associated with other metabolic syndromes, including hypertension, dyslipidemias and polycystic ovarian syndrome (PCOS). Recent advances have demonstrated that pharmacological agents of the thiazolidinedione class can reverse insulin resistance and profoundly improve many of these associated symptoms. These effects have been documented in a variety of genetic and acquired animal models of insulin resistance, as well as in numerous clinical trials in patients with insulin resistance. These compounds appear to enhance insulin action by modulating the activity of the nuclear receptor peroxisome proliferator-activated receptor (PPAR) gamma. This activation results in changes in the expression of a number of genes that are critically involved in glucose and lipid metabolism, as well as in insulin signal transduction. While precise events that occur downstream from PPAR gamma modulation remain uncertain, new insights are emerging from knockout studies in mice and the identification of genetic variants in humans. These findings indicate that there is still much to learn about the molecular biology and physiology of these interesting receptors, and that research in this area can lead to more effective and safer drugs to treat insulin resistance and associated syndromes.
Article
Adiponectin is a collagen-like circulating protein secreted by adipocytes that is proposed to mediate obesity-related resistance to insulin. In a case-control series, we assessed the role of adiponectin in later development of type 2 diabetes in 70 patients who later developed type 2 diabetes and 70 controls, matched for body-mass index, age, and sex. Cases and controls were taken from the longitudinal study of health in the Pima Indian population. At baseline, the concentration of adiponectin was lower in cases than in controls (p=0.01) and individuals with high concentrations of this protein were less likely to develop type 2 diabetes than those with low concentrations (incidence rate ratio 0.63 [95% CI 0.43-0.92]; p=0.02).
Article
Cardiovascular disease (CVD) is the most common complication of type 2 diabetes. However, CVD risk factors are elevated long before the development of diabetes,1 and the development of CVD can also precede the clinical diagnosis of type 2 diabetes.2 The close relationship between diabetes and CVD has led to the “common-soil” hypothesis,3 postulating that type 2 diabetes and CVD share common genetic and environmental antecedents, ie, “they spring from a common soil.” The hypothesis implies that atherosclerosis might not be simply a consequence of diabetes but that diabetes and CVD are a single entity sharing an underlying pathophysiology. See page 1845 Multiple lines of evidence support the common-soil hypothesis. In epidemiologic studies, the same set of diet and lifestyle factors (a diet higher in glycemic load and trans fat and lower in fiber and polyunsaturated fat, smoking, overweight and obesity, lack of regular exercise, and abstinence from alcohol) explains more than 80% of cases of coronary heart disease4 and 90% of cases of type 2 diabetes.5 Low birth weight, a marker of intrauterine nutritional deficiency, has been associated with increased risk of both diabetes and CVD in later life.6 In addition, pharmacological and lifestyle strategies to prevent type 2 diabetes have resulted in significant reductions in the occurrence of the metabolic syndrome and cardiovascular risk factors in subjects with impaired glucose tolerance,7 although it remains to be …
Article
Adipose tIssue regulates insulin sensitivity via the circulating adipocytokines, leptin, resistin and adiponectin. The objective of this study was to compare the levels of resistin, adiponectin and leptin in lean and obese subjects and determine the relationship between circulating adipocytokines and insulin resistance. We examined plasma levels of resistin, adiponectin and leptin in 17 lean subjects with a mean body mass index (BMI) of approximately 23 and 34 non-diabetic obese individuals with a mean BMI approximately 33. Insulin resistance was assessed using the homeostasis model assessment ratio (HOMA-R) formula derived from fasting insulin and glucose levels. Resistin levels were not significantly different between the two groups but were significantly higher in women compared with men, 35.4+/-6.5 (s.e.) vs 15.4+/-2.9 microg/L, P<0.01. Resistin did not correlate with BMI but did significantly correlate with HOMA-R, P<0.01, and this correlation remained significant after adjustment for gender and BMI. Adiponectin levels were significantly lower in obese compared with lean subjects, P<0.005, and higher in women, P<0.001, but showed no significant correlation with HOMA-R. Leptin levels were significantly higher in obese subjects and women and correlated with HOMA-R and resistin. In this small group of patients we demonstrated that insulin resistance correlated most strongly with leptin levels. A significant correlation between resistin levels and insulin resistance was also observed. Although a similar trend was apparent for adiponectin, the correlation with insulin resistance did not achieve statistical significance.
Article
Nearly unlimited supplies of energy-dense foods and technologies that encourage sedentary behaviour have introduced a new threat to the survival of our species: obesity and its co-morbidities. Foremost among the co-morbidities is type 2 diabetes, which is projected to afflict 300 million people worldwide by 2020. Compliance with lifestyle modifications such as reduced caloric intake and increased physical activity has proved to be difficult for the general population, meaning that pharmacological intervention may be the only recourse for some. This epidemiological reality heightens the urgency for gaining a deeper understanding of the processes that cause metabolic failure of key tissues and organ systems in type 2 diabetes, as reviewed here.
The intervention effect of marine collagen peptide on atherosclerosis, cardiac struction in hypertension patients
  • C F Zhu
  • F Zhang
  • J X Zhou
  • Y Chen
  • L Liu
  • Y R Sun
  • J Q Yuan
  • Y Li
  • CF Zhu
Marine collagen peptide in patients with hypertension fat intervention on the expression of endocrine hormones
  • C F Zhu
  • Z L Guan
  • H B Peng
  • CF Zhu
Effect of marine collagen peptide on the expression of overoxidation stress markers in rats with type 2 diabetes
  • G Q Liu
  • C F Zhu
  • Y F Li
  • GQ Liu