Article

Therapeutic Evaluation of the Effect of Biotin on Hyperglycemia in Patients with Non-Insulin Dependent Diabetes Mellitus.

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Abstract

The therapeutic efficacy of biotin was evaluated in 43 patients with non-insulin dependent diabetes mellitus. The serum biotin concentration in the patients was significantly lower than that in the 64 healthy control subjects and inversely correlated with the fasting blood glucose level. The oral administration of biotin, 9mg daily, corrected the hyperglycemia in the patients with no change in their serum insulin level. The serum levels of pyruvate and lactate decreased to their normal ranges after the administration. These observations suggest that the biotin administration ameliorates abnormal glucose metabolism in diabetic patients, presumably by enhancing the activity of the biotin-dependent enzyme, pyruvate carboxylase, with a subsequent promotion of glucose utilization for the entry into the tricarboxylic acid cycle. The administration also enhanced the response to glibenclamide in patients who had been resistant to the agent, suggesting a significant increase in the potency of the endogenous insulin action. The result demonstrates that biotin administration is effective for the treatment of the patients. Neither a relapse of clinical symptoms nor an occurrence of undesirable side effects has been observed.

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... In reference to the latter, the vitamin has been shown to increases the expression of pancre-atic and duodenal homeobox 1 (Pdx-1) (44), a critical transcription factor for the expression of insulin, and several genes involved in its synthesis and secretion by pancreatic beta cells (2). In pancreatic beta cells, biotin appears to increase the expression of insulin receptor (7) and glucokinase (3,30,39), a rate-limiting enzyme in glucose-stimulated insulin secretion (20). It also decreases the expression of several gluconeogenic genes (6,36). ...
... It also decreases the expression of several gluconeogenic genes (6,36). Finally, biotin supplementation appears to have the ability to reduce hyperglycemia and improve glucose tolerance in humans (5,15,20), as well as in animal models of diabetes (26,46). ...
... The pancreas was isolated, minced, and digested with collagenase IV (1 mg/ml) containing DNase I (0.1 mg/ml) for 30 min with occasional shaking at 37°C. After digestion, pancreatic tissues were filtered through nylon mesh and the filtrate was subjected to discontinuous Ficoll gradient (25,23,20, and 11%, respectively) for isolation of islets. Islets were collected from the interface of 20 and 11% of Ficoll, subsequently washed three times, and used for uptake studies as described before (23). ...
Article
Biotin is essential for the normal function of pancreatic beta cells. These cells obtain biotin from their surroundings via transport across their cell membrane. Little is known about the uptake mechanism involved, how it is regulated, and how it is affected by internal and external factors. We addressed these issues using the mouse-derived pancreatic beta-TC-6 cells and freshly isolated mouse and human primary pancreatic beta cells as models. The results showed biotin uptake by pancreatic beta-TC-6 cells occurs via a Na(+) - dependent, carrier-mediated process, that is sensitive to desthiobiotin, as well as to pantothenic acid, and lipoate; the process is also saturable as a function of concentration (apparent Km = 22.24 ± 5.5 µM). These cells express the sodium-dependent multivitamin transporter (SMVT), whose knockdown (with doxycycline - inducible shRNA) led to a sever inhibition in biotin uptake. Similarly, uptake of biotin by mouse and human primary pancreatic islets is Na(+)-dependent and carrier-mediated, and both cell types express SMVT. Biotin uptake by pancreatic beta-TC-6 cells is also adaptively regulated (via transcriptional mechanism) by extracellular substrate level. Chronic treatment of pancreatic beta-TC-6 cells with bacterial lipopolysaccharides (LPS) leads to inhibition in biotin uptake. This inhibition is mediated via a Toll-Like receptor 4 -mediated process, and involves a decrease in membrane expression of SMVT. These findings show, for the first time, that pancreatic beta cells/islets take up biotin via a specific and regulated carrier-mediated process, and that the process is sensitive to the effect of LPS.
... Biotin status has also been found to be altered in diabetic patients. Maebashi et al (4) found that serum biotin concentrations in type 2 diabetic patients were significantly lower than those in control subjects. An inverse correlation between serum biotin and fasting blood glucose concentrations has also been observed (4,5). ...
... Maebashi et al (4) found that serum biotin concentrations in type 2 diabetic patients were significantly lower than those in control subjects. An inverse correlation between serum biotin and fasting blood glucose concentrations has also been observed (4,5). Furthermore, biotin deficiency has been linked to impaired oral-glucose-tolerance tests and decreased utilization of glucose in rats (6,7). ...
... In addition, the diabetic state appears to be ameliorated by biotin treatment. Hyperglycemia reduction was observed in both type 1 and type 2 diabetic subjects treated with biotin (4,5). In hemodialysis patients, pharmacologic doses of biotin improve their oral-glucose-tolerance tests (8). ...
... The findings that biotin has stimulatory effects on the transcription of genes whose action favors glycemia reduction and decreases the transcription of gluconeogenic genes support other observations that indicate that pharmacological doses of biotin decrease hyperglycemia [26][27][28][29][30]. In genetically diabetic KK mice and in OLETF rats, biotin treatment lowered postprandial glucose concentration and improved tolerance to glucose [26,27]. ...
... In genetically diabetic KK mice and in OLETF rats, biotin treatment lowered postprandial glucose concentration and improved tolerance to glucose [26,27]. Hyperglycemia reduction was also observed in both type 1 and type 2 diabetics treated with biotin [28,29]. In hemodialysis patients, pharmacological doses of biotin improved their oral glucose tolerance tests [30]. ...
... Several studies have demonstrated that biotin deficiency affects glucose metabolism [18,19,22,24,25], indicating that biotin dietary intake is required to maintain glucose homeostasis. On the other hand, pharmacological doses of biotin (milligrams) favor glucose homeostasis [26][27][28][29][30] and are currently used in the treatment of diabetes [31,32]. Pharmacologic supplementation of biotin of 40× the RDI (i.e., 1.2 mg/day) for 14 days reaches serum concentrations in a range of 9.4-47.7 nmol/L [60]. ...
... Biotin (vitamin B 7 ) serves as a cofactor for carboxylase enzymes in fatty acid synthetic pathways, the citric acid cycle, and amino acid metabolism (Fernandez-Mejia, 2005). Type 2 diabetics have demonstrated lower circulating levels of biotin compared to healthy controls and an inverse relationship between biotin levels and fasting plasma glucose (Coggeshall, Heggers, Robson, & Baker, 1985;Maebashi et al., 1993). ...
... Diabetic patients treated for 28 days with 15 mg of biotin supplements had improvements in fasting glucose and insulin levels (Fernandez-Mejia, 2005; Fernandez-Mejia, Zendejas-Ruiz, Revilla-Monsalve, & Islas-Andrede, 2003). One study showed that patients with type 2 diabetes have reduced serum concentrations of biotin and that a 30-day supplementation improved fasting glucose (Maebashi et al., 1993). The clinical utility of B-group vitamins like nicotinamide and biotin still needs to be established as they may play an important role in glycemic control for type 2 diabetics. ...
... Pharmacological doses of biotin have hypolipidemic [4][5][6][7][8] and hypoglycemic effects [7,[9][10][11][12] and reduce diabetes complications [11][12][13] in both animal models and humans. These effects are associated with changes in gene and protein expression [12,[14][15][16][17][18] in key metabolic organs, such as the liver and the pancreatic islets. ...
... In humans, no adverse effects were found with administration of 0.25 to 100 mg biotin. A lack of adverse effects has been reported in patients with inborn errors of biotin metabolism [46], normal individuals [24], diabetic patients [10,13], and patients undergoing hemodialysis [11]. Rats fed diets containing up to 1,000 mg/kg diet did not show liver damage [21]. ...
Article
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Pharmacological concentrations of biotin have pleiotropic effects. Several reports have documented that biotin supplementation decreases hyperglycemia. We have shown that a biotin-supplemented diet increased insulin secretion and the mRNA abundance of proteins regulating insulin transcription and secretion. We also found enlarged pancreatic islets and modified islet morphology. Other studies have shown that pharmacological concentrations of biotin modify tissue structure. Although biotin administration is considered safe, little attention has been given to its effect on tissue structure. In this study, we investigated the effect of biotin supplementation on hepatic morphology and liver toxicity markers. Male BALB/cAnN Hsd mice were fed a control or a biotin-supplemented diet for 8 weeks. Versus the control mice, biotin-supplemented mice had an altered portal triad with dilated sinusoids, increased vascularity, and bile conducts. Furthermore, we observed an increased proportion of nucleomegaly and binucleated hepatocytes. In spite of the liver morphological changes, no differences were observed in the serum liver damage indicators, oxidative stress markers, or antioxidant enzymes. Our data demonstrate for the first time that biotin supplementation affects liver morphology in normal mice, and that these modifications are not paralleled with damage markers.
... Biotin (vitamin B 7 ) serves as a cofactor for carboxylase enzymes in fatty acid synthetic pathways, the citric acid cycle, and amino acid metabolism (Fernandez-Mejia, 2005). Type 2 diabetics have demonstrated lower circulating levels of biotin compared to healthy controls and an inverse relationship between biotin levels and fasting plasma glucose (Coggeshall, Heggers, Robson, & Baker, 1985;Maebashi et al., 1993). ...
... Diabetic patients treated for 28 days with 15 mg of biotin supplements had improvements in fasting glucose and insulin levels (Fernandez-Mejia, 2005; Fernandez-Mejia, Zendejas-Ruiz, Revilla-Monsalve, & Islas-Andrede, 2003). One study showed that patients with type 2 diabetes have reduced serum concentrations of biotin and that a 30-day supplementation improved fasting glucose (Maebashi et al., 1993). The clinical utility of B-group vitamins like nicotinamide and biotin still needs to be established as they may play an important role in glycemic control for type 2 diabetics. ...
Article
With global aging population, age-related cognitive decline becomes epidemic. Lifestyle-related factor is one of the key preventative measures. Dietary pattern analysis which considers dietary complexity has recently used to examine the linkage between nutrition and cognitive function. A priori approach defines dietary pattern based on existing knowledge. Results of several dietary pattern scores were summarized. The heterogeneity of assessment methods and outcome measurements lead to inconsistent results. Posteriori approach derives a dietary pattern independently of the existing nutrition-disease knowledge. It showed a dietary pattern abundant with plant-based food, oily fish, lower consumption of processed food, saturated fat, and simple sugar which appears to be beneficial to cognitive health. Despite inconclusive evidence from both approaches, diet and exercise, beneficial for other diseases, remains to be the two key modifiable factors for cognitive function. Large-scale prospective studies in multiethics population are required to provide stronger evidence in the future.
... (14) (15) Biotin also has shown beneficial effects in diabetic neuropathy , dyslipidemia associated with Type 2 DM in recent human trials. (16) (17)(18) Patients with Type 2 DM are also prone for nutritional deficiency of biotin manifesting as dermatitis , alopecia. So multiple benefits can be obtained by patients with Type 2 DM. ...
... [120][121][122][123][124][125] Moreover, it has been reported to aid glycaemic control both in animal models of diabetes and in diabetic patients, although favourable impacts on hepatocyte function also contribute in this regard. 126 ...
... Biotin, a nutraceutical agent, has been demonstrated through animal and clinical studies to have the capability of assisting in glycemic control in diabetic individuals if taken at a high dose of 9-15 mg per day (Zhang et al., 1996;Zhang et al., 1997;Maebashi et al., 1993). Various animal studies and few clinical studies established the effect of supplementary magnesium on the preservation of adipocyte insulin sensitivity (McCarty, 2005). ...
Article
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Background and Objective: Diabetes is an insidious as well as a debilitating metabolic disease with variety of causes that could lead to severe complications in multiple organs within the body system. There has been no documented scientific evidence as regards total cure of this complex chronic disease; therefore, it demands a lifelong management. This has necessitated the recent evaluation of several plant derived foods as costeffective alternatives in the management of diabetes and its associated complication.Materials and Methods: This review is based on integration of information from multi databases after a comprehensive literature search on the various plant derived foods that have been reported to have shown a certain degree of amelioration in the management of diabetes and diabetic complications.Result and Discussion: Published reports suggest that oxidative stress primarily mediated by uncontrolled hyperglycemia play a pivotal role in the pathogenesis of diabetes and its associated complications. Therefore, various plant-derived foods are believed to delay, prevent or manage diabetes and its associated complications using different mechanisms which could be established through their potential to increase insulin sensitivity, free radicals scavenging abilities, hypolipidemic, hypoglycaemic, hypocholesterolemic, antioxidative, anti-inflammatory and inhibition of α-amylase and α-glucosidase activities.Conclusion: Based on the evidence presented in this review, plant-derived foods possess bioactive constituents believed to be rich in antioxidants and proteins which may be responsible for their mode of actions; we propose that Cucuma longa (curcumin), Garcinia kola (kolaviron), Telfairia occidentalis and Parkia biglobosa be explored in the management of diabetes and its associated complications due to their outstanding beneficial effects.
... The role of biotin in improving skeletal muscle insulin sensitivity is not as well established. The majority of pre-clinical studies evaluating the mechanisms of biotin action with regard to lowering glucose have studied its effects on blood glucose, hepatocytes, and pancreatic beta cells (66)(67)(68)(69)(70)(71). However, hypotheses do exist that advocate for the role of biotin as a means to improve glucose uptake in skeletal muscle. ...
Article
Type 2 diabetes is a common metabolic disorder characterized by resistance to the actions of insulin to stimulate skeletal muscle glucose disposal. In light of the staggering financial/human cost of type 2 diabetes, there is considerable need for safe and effective agents that can be used to prevent and/or adjunctively treat the disease. Available evidence suggests that a number of natural supplements, including cinnamon, biotin, fenugreek, ginseng, banaba, and alpha-lipoic acid, have the potential to reduce the risk for type 2 diabetes in the large at-risk population. The evidence also suggests that, when used adjunctively, these natural products are likely to help clinicians achieve optimal glycemic control, improve long-term prognosis, and/or minimize the need for insulin therapy in type 2 diabetics. More research, particularly well-designed, long-term human clinical trials, is certainly needed to accurately define the value and place of these supplements in diabetes prevention and management.
... The recommended daily intake (RDI) of biotin is 30 g per day (1). Biotin doses up to 100 times the RDI are frequently encountered in nutritional supplements promoted for conditions such as type 2 diabetes mellitus (2) and are reported to be beneficial for skin and hair. High-dose biotin (10 000 times RDI) has been documented to improve clinical outcomes and quality of life in patients with secondary progressive multiple sclerosis (MS) (3,4). ...
Article
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Context: Biotin (Vitamin B7) is an essential co-factor for four carboxylases involved in fatty acid metabolism, leucine degradation and gluconeogenesis. The recommended daily intake (RDI) of biotin is approximately 30μ g per day. Low-moderate dose biotin is a common component of multivitamin preparations and high dose biotin (10,000 times RDI) has been reported to improve clinical outcomes and quality of life in patients with progressive multiple sclerosis. Biotin is also a component of immunoassays and supplementation may cause interference in both thyroid and non-thyroid immunoassays. Objective: To assess whether biotin ingestion caused abnormal thyroid function tests (TFTs) in a patient through assay interference Design: We report a patient with biotin-associated abnormal TFTs, and a systematic review of the literature Setting: A tertiary endocrine service in Hamilton, New Zealand Results: The patient had markedly abnormal thyroid function tests that did not match the clinical context. Following biotin cessation, TFTs normalised far more rapidly than possible given the half-life of thyroxine, consistent with assay interference by biotin. Multiple other analytes also tested abnormal in the presence of biotin. Conclusion: Biotin ingested in moderate to high doses can cause immunoassay interference. Depending on the assay format, biotin interference can result in either falsely high or low values. Interference is not limited to thyroid tests and has the potential to affect a wide range of analytes. It is important for clinicians to be aware of this interaction to prevent misdiagnosis and inappropriate treatment.
... These two significant pathways are biotin metabolism (map 00780) and vascular smooth muscle contraction (map 04270) (Xie et al., 2006;Hashimoto et al., 2020). For biotin metabolism, several studies have shown that plasma triacylglycerol, low-density lipoprotein cholesterol (LDL), and fasting glucose are reduced in patients with T2D who take biotin supplementation (Maebashi et al., 1993;Revilla-Monsalve et al., 2006). Furthermore, biotin intake has been reported to be effective in improving glycaemic control through diabetic animal models (Reddi et al., 1988;Zhang et al., 1997). ...
Article
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Integrative multi-omics analysis has become a useful tool to understand molecular mechanisms and drug discovery for treatment. Especially, the couplings of genetics to metabolomics have been performed to identify the associations between SNP and metabolite. However, while the importance of integrative pathway analysis is increasing, there are few approaches to utilize pathway information to analyze phenotypes using SNP and metabolite. We propose an integrative pathway analysis of SNP and metabolite data using a hierarchical structural component model considering the structural relationships of SNPs, metabolites, pathways, and phenotypes. The proposed method utilizes genome-wide association studies on metabolites and constructs the genetic risk scores for metabolites referred to as genetic metabolomic scores. It is based on the hierarchical model using the genetic metabolomic scores and pathways. Furthermore, this method adopts a ridge penalty to consider the correlations between genetic metabolomic scores and between pathways. We apply our method to the SNP and metabolite data from the Korean population to identify pathways associated with type 2 diabetes (T2D). Through this application, we identified well-known pathways associated with T2D, demonstrating that this method adds biological insights into disease-related pathways using genetic predispositions of metabolites.
... High-dose biotin appears to have the potential to rectify this situation to some degree. Presumably as a result of these effects, studies in rodent models of diabetes, as well as some pilot clinical trials in both types of diabetes, report that high-dose biotin can improve glycemic control [220,221,224,[227][228][229]. ...
Article
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Oxidative stress, the resulting uncoupling of endothelial nitric oxide synthase (eNOS), and loss of nitric oxide (NO) bioactivity, are key mediators of the vascular and microvascular complications of diabetes. Much of this oxidative stress arises from up-regulated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. Phycocyanobilin (PhyCB), the light-harvesting chromophore in edible cyanobacteria such as spirulina, is a biliverdin derivative that shares the ability of free bilirubin to inhibit certain isoforms of NADPH oxidase. Epidemiological studies reveal that diabetics with relatively elevated serum bilirubin are less likely to develop coronary disease or microvascular complications; this may reflect the ability of bilirubin to ward off these complications via inhibition of NADPH oxidase. Oral PhyCB may likewise have potential in this regard, and has been shown to protect diabetic mice from glomerulosclerosis. With respect to oxidant-mediated uncoupling of eNOS, high-dose folate can help to reverse this by modulating the oxidation status of the eNOS cofactor tetrahydrobiopterin (BH4). Oxidation of BH4 yields dihydrobiopterin (BH2), which competes with BH4 for binding to eNOS and promotes its uncoupling. The reduced intracellular metabolites of folate have versatile oxidant-scavenging activity that can prevent oxidation of BH4; concurrently, these metabolites promote induction of dihydrofolate reductase, which functions to reconvert BH2 to BH4, and hence alleviate the uncoupling of eNOS. The arginine metabolite asymmetric dimethylarginine (ADMA), typically elevated in diabetics, also uncouples eNOS by competitively inhibiting binding of arginine to eNOS; this effect is exacerbated by the increased expression of arginase that accompanies diabetes. These effects can be countered via supplementation with citrulline, which efficiently enhances tissue levels of arginine. With respect to the loss of NO bioactivity that contributes to diabetic complications, high dose biotin has the potential to "pinch hit" for diminished NO by direct activation of soluble guanylate cyclase (sGC). High-dose biotin also may aid glycemic control via modulatory effects on enzyme induction in hepatocytes and pancreatic beta cells. Taurine, which suppresses diabetic complications in rodents, has the potential to reverse the inactivating impact of oxidative stress on sGC by boosting synthesis of hydrogen sulfide. Hence, it is proposed that concurrent administration of PhyCB, citrulline, taurine, and supranutritional doses of folate and biotin may have considerable potential for prevention and control of diabetic complications. Such a regimen could also be complemented with antioxidants such as lipoic acid, N-acetylcysteine, and melatonin-that boost cellular expression of antioxidant enzymes and glutathione-as well as astaxanthin, zinc, and glycine. The development of appropriate functional foods might make it feasible for patients to use complex nutraceutical regimens of the sort suggested here.
... Not much research has been done biotin concentration in the type 2 diabetes patients controls and inversely correlated with the fasting blood glucose level. The oral administration of biotin, 9 mg daily, corrected the hyperglycaemia in patients with no change in their serum insulin level 62 . A study of biotin and chromium picolinate supplementation of type 2 diabetic rats has shown anti-diabetic effects 63 . ...
Article
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The present review evaluates the relationship between type 2 diabetes mellitus and vitamins. Oxidative stress has been implicated in the development of type 2 diabetes and its several complications. Antioxidant vitamins A, C and E are found decreased in type 2 diabetes and there is increasing evidence that antioxidants may have role not only in reducing development of diabetes and its complications, but also in improving glycemic control. Several B vitamins e.g. Thiamine, Pyridoxine, Biotin, B12 are also found decreased in type 2 diabetes. Thiamine has beneficial role in diabetic nephropathy while Pyridoxine may have a role in treatment of diabetic retinopathy. Metformin, when used for long term, has been found to cause deficiency of Folate and B12. Vitamin D deficiency is considered a risk factor for the development of type 2 diabetes as well as its complications particularly cardiovascular ones; moreover, vitamin D supplementation has favourable effects on glycaemia. There are no current recommendations of routine supplementation of vitamins above the recommended dietary allowances either to prevent development of type 2 diabetes or to improve outcomes in people with type 2 diabetes unless there is underlying deficiencies. However, patients taking metformin for long time may need folic acid and B12 supplementation.
... 58,67,[69][70][71] It has also been observed that compared with healthy controls, patients with diabetes have lower plasma concentrations of vitamin C 72 and lower circulating concentrations of biotin, with an inverse correlation between biotin status and fasting plasma glucose. 73,74 Low levels of serum vitamin D have been found to significantly increase cardiometabolic risk (including insulin resistance, metabolic syndrome, and cardiovascular disease risk), 75 and preliminary evidence suggests that vitamin D with or without calcium supplementation may improve glucose metabolism and insulin signaling. [76][77][78][79] Antidiabetic medications can also affect micronutrient status. ...
Article
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Objective: Prescription drug use is on the rise, and the use of dietary supplementation remains common. In the United States, more than half of all adults take a dietary supplement in any given month. As a result, drug-nutrient interactions are becoming an important consideration when pharmacists counsel patients about their drug regimens. We reviewed the literature to identify common and/or clinically relevant drug-nutrient interactions that pharmacists may encounter in practice. Data Sources: A MEDLINE search for English-language publications from 1970 through March 2017 was performed using search terms (and variations) related to drugs, medications, micronutrients, and interactions. Study Selection and Data Extraction: Relevant studies, case reports, and reviews describing drug-nutrient interactions were selected for inclusion. Data Synthesis: Some drug-nutrient interactions may result in micronutrient insufficiencies or even frank deficiencies, thereby necessitating augmentation with multivitamin/minerals or individual vitamin/mineral dietary supplements. This most often occurs with long-term therapy for chronic conditions, such as treatment with proton-pump inhibitors and histamine-2 receptor antagonists. In addition, some chronic diseases themselves, such as diabetes, may predispose patients to micronutrient insufficiencies, and dietary supplementation may be advisable. Conclusions: Drug-nutrient interactions can often be resolved through specific dosing strategies to ensure that the full effect of the medication or the dietary supplement is not compromised by the other. In rare cases, the dietary supplement may need to be discontinued or monitored during treatment. Pharmacists are in a key position to identify and discuss these drug-nutrient interactions with patients and the health care team.
... Although data are lacking on the incidence of biotin deficiency in patients with obesity or diabetes, it has been demonstrated that patients with type 2 diabetes have lower biotin levels compared with healthy controls and that these low plasma levels are associated with hyperglycaemia [8,146,147]. ...
Article
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Overweight and obesity are highly prevalent throughout the world and can adversely affect the nutritional status of individuals. Studies have shown that many people with obesity have inadequate intake of iron, calcium, magnesium, zinc, copper, folate and vitamins A and B12, likely as a result of poor diet quality. Nutritional inadequacies or deficiencies may also occur due to altered pharmacokinetics in the individual with obesity and due to interactions in those with overweight or obesity with various pharmaceuticals. However, it has been demonstrated that the adult population in the United States as a whole is deficient in certain micronutrients as a result of the availability and overconsumption of high-calorie, low-nutrient processed foods. Poor nutrition may contribute to the development of certain chronic conditions, such as type 2 diabetes, which is already more prevalent in those with obesity. Clinicians need to be aware of these gaps, particularly in those individuals with obesity who are undergoing bariatric surgery or taking pharmaceutical products long term to facilitate weight loss. Patients with overweight or obesity likely struggle to achieve a balanced diet and may benefit from consultation with a dietitian. Along with providing recommendations for healthy eating and exercise, supplementation with specific micronutrients or multivitamins should be considered for individuals at the highest risk for or with established deficiencies. Further research is needed to understand the factors underlying nutritional inadequacies in individuals with overweight or obesity, as well as the outcomes of treatment strategies employed to address them.
... When administered at doses of 300 mg/day, one clinical trial showed clinical improvement in 13 out of 103 patients with multiple sclerosis, versus none in the placebo control arm [12]. More modest levels of biotin supplementation have been shown to significantly reduce fasting glucose levels in patients with type 2 diabetes mellitus, as well as triglyceride levels in those with and without type 2 diabetes mellitus [13][14][15]. However, some of the results from these data are conflicting. ...
Article
A 67-year-old female with a past medical history of multiple endocrine issues presented for follow-up subsequent to abnormal routine blood testing results. These included low thyroid stimulating hormone (TSH), low parathyroid hormone (PTH), and mildly elevated calcium levels. The presence of hypercalcemia and accompanying low PTH raised the concern for malignancy, while the depressed TSH indicated hyperthyroidism. Review of the patient's medications revealed daily supplementation with 5 mg of vitamin B7 (biotin). The biotin was discontinued after suspecting the supplement was interfering with the patient's lab values. The labs were repeated one month later. The results showed normalized TSH, PTH, and calcium levels. The increasingly wide-spread use of biotin supplementation and the use of biotin as a component in many of the most common clinical assays has led to a trend of lab errors due to biotin interference. While some physicians are aware of the possibility of skewed results, steps need to be taken to prevent misdiagnosis. This includes ensuring that information about this issue is more widely disseminated, accurately accounting for a patient's supplement use, reconciling proper clinical correlation with lab results, and promptly reporting when biotin is determined to be the cause of otherwise unexplained lab errors.
... С целью улучшения функ ционального состояния β-клеток целесообразно его применение с биотином, который является серосодержащим соединением, учас твующим в качестве коэнзима в процессах карбоксилирования. Биотин также повышает экспрессию глюкокиназы в β-клетках, что, естественно, улучшает функциональную активность глицерол-3-дегидрогеназного шунта в β-клетках [26,27]. Не исключено, что применение биотина и СоQ10 в комплексной терапии сахарного диабета 2 типа будет способствовать также и снижению степени выраженности, а может быть и исчезновению так называемой резистентности β-клеток к сульфонилмочевинным препаратам (вторичная резистентность к сульфонилмочевинным препаратам), что часто наблюдается у больных сахарным диабетом 2 типа при длительном их применении. ...
... [12][13][14][15][16] Additionally, supplementation with high-dose biotin could be beneficial in the treatment of dermatitis, diabetes mellitus, and depression. [17][18][19][20][21][22] In pregnancy, supplementation of up to 300 lg biotin per day might be required, which should not interfere with current immunoassays. 17,22 Biotin is also very popular as a self-medication to reduce hair loss or to improve the condition of skin and nails in supraphysiological doses of up to 30 mg daily, and supplements containing as much as 100 mg of biotin are available overthe-counter. ...
Article
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Context.— Immunoassays using the interaction between streptavidin and biotin are used for clinical chemical analytes on platforms by many different manufacturers. The design can be susceptible to interference from high-dose biotin intake in patients, which remains an often-overlooked confounder despite recently increased awareness. Objective.— To evaluate an easily implementable method of in vitro biotin depletion for the removal of biotin interference in immunoassays for potentially time-critical analytes. Design.— A biotin stock solution was made and de-identified patient samples were spiked to reach a biotin concentration of 1.126 × 10 ⁶ pg/mL, the maximum reported biotin concentration 1 to 2 hours after a single oral dose of 300 mg biotin. Then, the resulting interference in Elecsys immunoassays for cortisol, cyclosporine A, tacrolimus, digitoxin, thyroid-stimulating hormone, free triiodothyronine, free thyroxine, C-peptide, insulin, N-terminal pro-B–type natriuretic peptide, troponin T high sensitive, human immunodeficiency virus, procalcitonin, β human chorionic gonadotropin, toxoplasma immunoglobulin M, and toxoplasma immunoglobulin G was evaluated before and after biotin depletion using streptavidin particles. Results.— All tested immunoassays, with the exception of toxoplasma immunoglobulin M and toxoplasma immunoglobulin G, suffered from significant biotin interference. The depletion protocol removed assay interference due to biotin and produced results that were close or identical to initial prespike measurements. Conclusions.— Despite an increase in turnaround times, biotin adsorption is a feasible countermeasure for biotin interference in Elecsys immunoassays. Until test kits with an increased resistance to the interference from high-dose biotin intake are distributed, the evaluated protocol can provide results properly reflecting the patient's clinical condition.
... Biotin supplementation modifies the expression of critical genes that are involved in the regulation of carbohydrate and lipid metabolism [8][9][10][11][12][13][14]. In agreement with these findings, several observations have indicated that biotin supplementation improves glucose and triglyceride homeostasis [15][16][17][18][19], which has led to the development of commercially available medications containing pharmacologically relevant amounts of biotin (2 mg/day) in combination with chromium picolinate [20,21]. ...
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Studies have found that biotin favors glucose and lipid metabolism, and medications containing biotin have been developed. Despite the use of biotin as a pharmacological agent, few studies have addressed toxicity aspects including the possible interaction with cytochrome P450 enzyme family. This study analyzed the effects of pharmacological doses of biotin on the expression and activity of the cytochrome P4501A subfamily involved in the metabolism of xenobiotics. Wistar rats were treated daily with biotin (2 mg/kg, i.p.), while the control groups were treated with saline. All of the rats were sacrificed by cervical dislocation after 1, 3, 5, or 7 days of treatment. CYP1A1 and CYP1A2 mRNAs were modified by biotin while enzyme activity and protein concentration were not affected. The lack of an effect of biotin on CYP1A activity was confirmed using other experimental strategies, including (i) cotreatment of the animals with biotin and a known CYP1A inducer; (ii) the addition of biotin to the reaction mixtures for the measurement of CYP1A1 and CYP1A2 activities; and (iii) the use of an S9 mixture that was prepared from control and biotin-treated rats to analyze the activation of benzo[a]pyrene (BaP) into mutagenic metabolites using the Ames test. The results suggest that biotin does not influence the CYP1A-mediated metabolism of xenobiotics.
... Biotin supplementation modifies the expression of critical genes that are involved in the regulation of carbohydrate and lipid metabolism [8][9][10][11][12][13][14]. In agreement with these findings, several observations have indicated that biotin supplementation improves glucose and triglyceride homeostasis [15][16][17][18][19], which has led to the development of commercially available medications containing pharmacologically relevant amounts of biotin (2 mg/day) in combination with chromium picolinate [20,21]. ...
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Studies have found that biotin favors glucose and lipid metabolism, and medications containing biotin have been developed. Despite the use of biotin as a pharmacological agent, few studies have addressed toxicity aspects including the possible interaction with cytochrome P450 enzyme family. This study analyzed the effects of pharmacological doses of biotin on the expression and activity of the cytochrome P4501A subfamily involved in the metabolism of xenobiotics. Wistar rats were treated daily with biotin (2 mg/kg, i.p.), while the control groups were treated with saline. All of the rats were sacrificed by cervical dislocation after 1, 3, 5, or 7 days of treatment. CYP1A1 and CYP1A2 mRNAs were modified by biotin while enzyme activity and protein concentration were not affected. The lack of an effect of biotin on CYP1A activity was confirmed using other experimental strategies, including (i) cotreatment of the animals with biotin and a known CYP1A inducer; (ii) the addition of biotin to the reaction mixtures for the measurement of CYP1A1 and CYP1A2 activities; and (iii) the use of an S9 mixture that was prepared from control and biotin-treated rats to analyze the activation of benzo[a]pyrene (BaP) into mutagenic metabolites using the Ames test. The results suggest that biotin does not influence the CYP1A-mediated metabolism of xenobiotics.
... In humans, biotin is needed for normal development, growth, and health. Studies have shown that it may help treat or prevent specific disorders such as alopecia, biotin-responsive basal ganglia disease, congenital anomalies, multiple sclerosis, onychorrhexis (brittle fingernails), photoaging, and Type 2 diabetes (Alfadhel et al., 2013;Chessa et al., 2019;Famenini and Goh, 2014;Komorowski et al., 2019a,b;Maebashi et al., 1993;Mock, 2009;Sedel et al., 2015Sedel et al., , 2016. Furthermore, a number of genetic disorders associated with secondary biotin deficiency including biotinidase deficiency, holocarboxylase synthetase deficiency, and biotin transport deficiency are treated with supplemental biotin (Wolf, 2012;Elrefai and Wolf, 2015;Mardach et al., 2002). ...
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A novel, highly soluble biotin salt, magnesium biotinate (MgB), was assessed for general and genetic toxicity using several toxicologic tests. This battery of tests included in vitro bacterial reverse mutation test, in vitro mammalian micronucleus assay, and oral acute, 14-day, and 90-day repeat-dose toxicity in Sprague-Dawley (SD) rats. The results of the in vitro studies indicate that MgB is not mutagenic, clastogenic, or aneugenic. The acute oral toxicity study established an LD50 ≥ 5000 mg MgB/kg. In the 14-day oral toxicity study, doses of MgB up to 2500 mg MgB/kg/day produced no clinical signs or mortality. In the 90-day oral toxicity study, administration of 600 mg MgB/kg/day resulted in no clinical signs and was determined to be the no-observed-adverse-effect-level (NOAEL), which equates to 39 g biotin/day for a 70 kg human. Since MgB is composed of 93% biotin, the 600 mg NOAEL equates to approximately 1.3 million times the current recommended daily allowance of 30 μg biotin/day and 3,900 times supplement levels of 10 mg biotin/day. Based on the toxicologic profile and lack of findings in various in vitro and in vivo studies, MgB may be considered safe for long-term human use.
... After the meal, even the glycemic action type of a body can be affected by its gut microbiota composition (Zeevi et al., 2015;Mendes-Soares et al., 2019). Some studies show that biotin deficiency may be associated with T2D (Maebashi et al., 1993;Wu et al., 2020) and biotin supplementation may help glucose regulation (Fernandez-Mejia, 2005;Albarracin et al., 2008;Lazo de la Vega-Monroy et al., 2013). ...
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... 19 Another B vitamin, vitamin B7 (biotin), has been shown to be decreased in subjects with moderate obesity 21 and type 2 diabetes. 22 Yet this vitamin has been neglected in the con- In addition to those metabolic observations regarding vitamin D, many studies also reported strong links of this vitamin with adipose tissue in terms of vitamin D storage but also modulation of adipocyte differentiation or even energy metabolism and inflammation by this vitamin. ...
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... Thus, in vivo biotin supplementation augmented beta cell proportion as well as beta cell function. Conversely, it has been reported that the circulating biotin level is lower in type 2 diabetic patients compared with normoglycemic individuals (Maebashi et al. 1993). Supplementation of biotin plus chromium improved glucose me-tabolism and glycemic control in clinical trials involving type 2 diabetic patients (Singer and Geohas 2006;Albarracin et al. 2008), and also improved atherogenic risk factors and serum lipids in both diabetic and non-diabetic individuals (Albarracin et al. 2007;Geohas et al. 2007;Revilla-Monsalve et al. 2006). ...
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During the last few decades, an increasing number of vitamin–mediated effects has been discovered at the level of gene expression in addition to their well–known roles as substrates and cofactors; the best recognized examples are the lipophilic vitamins A and D. Although little is known about water–soluble vitamins as genetic modulators, there are increasing examples of their effect on gene expression. Biotin is a hydro soluble vitamin that acts as a prosthetic group of carboxylases. Besides its role as carboxylase cofactor, biotin affects several systemic functions such as development, immunity and metabolism. In recent years, significant progress has been made in the identification of genes that are affected by biotin at the transcriptional and post–transcriptional levels as well as in the elucidation of mechanisms that mediate the effects of biotin on the gene expression. These studies bring new insights into biotin mediated gene expression and will lead to a better under–standing of biotin roles in the metabolism and in systemic functions.
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Understanding the molecular mechanisms of vitamins has opened new perspectives regarding the relationship between nutritional signals and biological functions, which, in turn, has led to the development of new therapeutic agents. Although little is known about water-soluble vitamins as genetic modulators, evidence about their effects on gene expression has grown. In the case of biotin, besides its role as a carboxylase prosthetic group, it also affects gene expression and has a wide repertoire of effects on biological functions. Only recently, the role of pharmacological concentrations of biotin on systemic functions has attracted attention, and it is now being reconsidered with the help of new technologies. This novel approach could lead to new perspectives in its use as a therapeutic agent. The present review is focused on the effects of pharmacological concentrations of biotin on several biological functions and on the biotin signaling pathways that participate in gene expression.
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(+)-Biotin was synthesized in 11 steps and in 25% overall yield from readily accessible l-cysteine through a Lewis base-catalyzed highly diastereoselective cyanosilylation of (2R,4R)-N-Boc-2-phenylthiazolidine-4-carbaldehyde 2 and a ring closure of a cis-allylic carbonate 5b utilizing a palladium-catalyzed intramolecular allylic amination.
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The course of our investigation to develop an industrially viable total synthesis of (+)-biotin is described. Three synthetic approaches to (+)-biotin have been investigated to develop an efficient synthetic method using L-cysteine and thiolactone as a starting material and a key intermediate, respectively. Short steps, high yield and ease of operation of the approach would permit the hitherto most efficient access to (+)-biotin.
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A novel and convenient method for the stereoselective synthesis of d-biotin 1 starting from the commercially available cis-1,3-dibenzyl-2-imidazolidone-4,5-dicarboxylic acid 2 has been developed. The key features of this synthesis include the enantioselective reduction of a meso-cyclic imide, mediated by a chiral oxazborolidine catalyst, derived from (1S,2S)-(+)-threo-1-(4-nitrophenyl)-2-amino-1,3-propanediol and the direct introduction of a C5 side chain to the (3aS,6aR)-thiolactone through a modified di-Grignard reaction. Enantioselectivities of 98% in the oxazborolidine-catalyzed asymmetric reduction process have been achieved.
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A synthesis of 2-epi-biotin sulfone was accomplished from commercially available l-cysteine. The synthesis features an unprecedented tandem S,N-carbonyl migration/aza-Michael/spirocyclization reaction from an l-cysteine-derived enone with aq. ammonia, in which three new sigma bonds and two rings are formed. In addition, the synthesis includes a highly diastereoselective late-stage Haller-Bauer reaction of sulfone for direct introduction of the carbon side chain.
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A cluster of inter-related conditions such as central obesity, dyslipidemia, impaired glucose metabolism, and hypertension is referred to as Metabolic Syndrome, which is a risk factor for the development of type-2 diabetes. The micro- and macro-vascular complications of diabetes contribute to its morbidity and mortality. In addition to its calcitropic effect, vitamin D is a regulator of gene expression as well as cell proliferation and differentiation. Various cross-sectional and longitudinal cohort studies have indicated a beneficial effect from vitamin D supplementation on the development of type-2 diabetes. Binding of retinol-bound retinol-binding protein to a membrane-binding protein suppresses insulin signaling. All-trans retinoic acid, a derivative of vitamin A, reverses these effects, resulting in increased insulin sensitivity, suppression of the phosphoenolpyruvate carboxy kinase (PEPCK) gene, and the induction of the glucokinase gene. Glucokinase and PEPCK are also regulated in opposite directions by the vitamin biotin, acting at the transcriptional level. Biotin also regulates the synthesis of insulin by the islet of Langerhans cells of the pancreas. The increase in advanced glycation end products (AGEs) is implicated in the initiation and progression of diabetes-associated microvascular diseases. Benfotiamine, a derivative of thiamine, and pyridoxamine, a vitamer of vitamin B6, both have anti-AGE properties, making them valuable therapeutic adjuvants in the treatment of diabetic complications. Thus, various vitamins and their derivatives have profound therapeutic potential in the prevention and treatment of type-2 diabetes.
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Background: Biotin acts as a coenzyme for carboxylases regulating lipid and amino acid metabolism. We investigated alterations of the biotin-dependent functions in obesity and the downstream effects of biotin restriction in adipocytes in vitro. Subjects: 24 monozygotic twin pairs discordant for BMI. Mean within-pair difference (heavy-lean co-twin, Δ) of BMI was 6.0 kg/m(2) (range 3.1-15.2 kg/m(2)). Methods: Adipose tissue (AT) DNA methylation, gene expression of AT and adipocytes, and leucocytes (RT-qPCR), serum biotin, C-reactive protein (CRP) and triglycerides were measured in the twins. Human adipocytes were cultured in low and control biotin concentrations and analyzed for lipid droplet content, mitochondrial morphology and mitochondrial respiration. Results: The gene expressions of carboxylases PCCB and MCCC1 were upregulated in the heavier co-twins' leucocytes. ΔPCCB (r=0.91, P=0.0046) and ΔMCCC1 (r=0.79, P=0.036) correlated with ΔCRP within-pairs. Serum biotin levels were lower in the heavier (274 ng/l) than in the lean co-twins (390 ng/l, P=0.034). ΔBiotin correlated negatively with Δtriglycerides (r=-0.56, P=0.045) within-pairs. In AT HLCS and ACACB were hypermethylated and biotin cycle genes HLCS and BTD were downregulated (P<0.05). Biotin-dependent carboxylases were downregulated (ACACA, ACACB, PCCB, MCCC2, and PC, P<0.05) in both AT and adipocytes of the heavier co-twins. Adipocytes cultured in low biotin had decreased lipid accumulation, altered mitochondrial morphology and deficient mitochondrial respiration. Conclusions: Biotin-dependent functions are modified by adiposity independent of genetic effects, and correlate with inflammation and hypertriglyceridemia. Biotin restriction decreases lipid accumulation and respiration, and alters mitochondrial morphology in adipocytes.International Journal of Obesity accepted article preview online, 25 November 2015. doi:10.1038/ijo.2015.237.
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Two scalable chemical processes for the cinchona alkaloid catalyst recovery were demonstrated. In the first approach, the organocatalyst quinine was removed first as the neutral tartrate from alcohol, one recrystallization giving pure salt. Quinine was then recovered in 95 % yield by basification of its aqueous tartrate salt and could be reused without any further purification. In the second approach, the pure quinine catalyst could be easily obtained in almost quantitative yield and with 99 % chemical purity after a single recrystallization from toluene and its spectral data (1H NMR and the value of specific rotation) were in agreement with those of the literature previously reported. The methods are versatile and applicable for industrial-scale synthesis of biologically relevant substance (+)-biotin.
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Development of a simple electrochemical immunosensor, for the direct detection of biotin, is important for monitoring biotin content. A displacement assay was used in biotin detection, in which surface-bound antibodies were dissociated from the surface of immunosensor in the presence of free biotin. Pre-treatment of samples is not required for biotin detection using this electrochemical immunosensor. Using this electrochemical immunosensor, the recoveries of biotin in the two infant formulas A and B were 93.9% and 91.3%, respectively, of their biotin concentrations as stated on their packaging. The direct detection of biotin, with this electrochemical immunosensor, in supplements X, Y, and Z, showed recoveries as high as 92.9%, 106.5%, and 100.0%, respectively. The accuracy of our electrochemical immunosensor was validated with high pressure liquid chromatography (HPLC). The surface of immunosensor had a strong anti-fouling property and high specificity for actual applications in complex matrices. Additionally, the developed immunosensor shows good stability, reproducibility, and intra- and inter-day precision. This electrochemical immunosensor can directly detect biotin in infant formulas, biotin-containing supplements, and serum.
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Objective Despite increasing evidence that pharmacological concentrations of biotin modify glucose metabolism, no studies have addressed the effects of biotin supplementation on glucagon production and secretion, considering glucagon is one of the major hormones in maintaining glucose homeostasis. In the present study, we investigated the effects of dietary biotin supplementation on glucagon expression, secretion, and action. Research Methods & Procedures Male BALB/cAnN Hsd mice were fed a control or a biotin-supplemented diet (1.76 or 97.7 mg biotin/kg diet) for eight weeks post-weaning. Glucagon gene mRNA expression was measured by the real-time polymerase chain reaction. Glucagon secretion was assessed in isolated islets and by glucagon concentration in plasma. Glucagon action was evaluated by glucagon tolerance tests, phosphoenolpyruvate carboxykinase (Pck1) mRNA expression, and glycogen degradation. Results Compared to the control group, glucagon mRNA and secretion were increased from the islets of the biotin-supplemented group. Fasting plasma glucagon levels were higher, but no differences between the groups were observed in non-fasting glucagon levels. Despite the elevated fasting glucagon levels, no differences were found in fasting blood glucose concentrations, fasting/fasting-refeeding glucagon tolerance tests, glycogen content and degradation, or mRNA expression of the hepatic gluconeogenic rate limiting enzyme, Pck1. Conclusions These results demonstrated that dietary biotin supplementation increased glucagon expression and secretion without affecting fasting blood glucose concentrations or glucagon tolerance and provided new insights into the effect of biotin supplementation on glucagon production and action.
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One of the most common micronutrient deficiencies with cutaneous findings is the vitamin B, also known as biotin, deficiency. Biotin deficiency may be due to congenital lack of biotinidase, or acquired following some conditions that interfere with its absorption, such as inflammatory bowel disorders, a diet too rich in avidin, magnesium deficiency, smoking habit and treatment with broad-spectrum antibiotics, anticonvulsants and sulfonamides. This review highlights the role of biotin in the most common skin disorders such associated with biotin deficiency and an approach to their treatment. Biotin administration may improve the treatment of hair loss when deficiency is detected on the basis of a careful patient history, clinical examination and the determination of serum biotin levels. The use of biotin is rationale in seborrheic dermatitis as the vitamin intercepts the main metabolic pathways underlying the pathogenesis of the disease. Treatment with biotin could also be useful in comedonal acne characterized by a high rate of seborrhea, and may be helpful for acne treated with topical retinoids, contributing to the control of flaking and irritation. The tolerability of biotin is excellent and there is no risk of hypervitaminosis even in the case of high doses. It is important that administration is controlled by physicians and follows a medical diagnosis and prescription. Correct doses used in dermatological conditions are safe and are not at risk of interference with laboratory tests.
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Tissue-specific metabolism determines their functions that collectively sense and respond to numerous stress cues to achieve systemic homeostasis. Chronic stress skews such metabolic profiles and leads to failure of organs as evidenced by a bias towards lipid synthesis and storage in the aging brain, muscle, and liver under Alzheimer's disease, sarcopenia, and non-alcoholic fatty liver disease, respectively. In contrast, the tissue destined for lipid synthesis and storage such as adipose limits its threshold and develops diabetes mellitus. However, the underlying factors that contribute to this lipogenic shift between organs are unknown. From this perspective, a differential biotin utilization between lipid-rich tissues such as adipose and brain during aging was hypothesized owing to the established role of biotin in lipogenesis. The same was tested using young and aged Wistar rats. We found that adipose-specific biotin content was much higher than the brain irrespective of aging status as well as its associated cues. However, within tissues, the adipose fails to maintain its biotinylation levels during aging whereas the brain seizes more biotin and exhibits lipid accumulation. Furthermore, mimicking the age-related stress cues in vitro such as high glucose and endoplasmic reticulum stress deprive the astroglial biotin content, but not that of adipocytes. Lipid accumulation in the aging brain was also correlated with increased S-adenosylmethionine levels and biotin utilization by astrocytes. In summary, differential biotin utilization between adipose and brain under aging and their respective cell types like adipocytes and astrocytes under age-associated stress cues connects well with the lipogenic shift in rat brain.
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The link between the gut microbiota and type 2 diabetes (T2D) warrants further investigation because of known confounding effects from antidiabetic treatment. Here, we profiled the gut microbiota in a discovery (n = 1,011) and validation (n = 484) cohort comprising Swedish subjects naive for diabetes treatment and grouped by glycemic status. We observed that overall gut microbiota composition was altered in groups with impaired glucose tolerance, combined glucose intolerance and T2D, but not in those with impaired fasting glucose. In addition, the abundance of several butyrate producers and functional potential for butyrate production were decreased both in prediabetes and T2D groups. Multivariate analyses and machine learning microbiome models indicated that insulin resistance was strongly associated with microbial variations. Therefore, our study indicates that the gut microbiota represents an important modifiable factor to consider when developing precision medicine approaches for the prevention and/or delay of T2D.
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Supplements containing pharmacological concentrations of biotin are commercially available. The mechanisms by which biotin at pharmacological concentrations exerts its action have been the subject of multiple investigations, particularly for biotin's medicinal potential and wide use for cosmetic purposes. Several studies have reported that biotin supplementation increases cell proliferation; however, the mechanisms involved in this effect have not yet been characterized. In a previous study, we found that a biotin-supplemented diet increased spermatogonia proliferation. The present study was focused on investigating the molecular mechanisms involved in biotin-induced testis cell proliferation. Male BALB/cAnNHsd mice were fed a control or a biotin-supplemented diet (1.76 or 97.7 mg biotin/kg diet) for eight weeks. Compared with the control group, the biotin-supplemented mice presented augmented protein abundance of the c-kit-receptor and pERK1/2Tyr204 and pAKTSer473, the active forms of ERK/AKT proliferation signaling pathways. No changes were observed in the testis expression of the stem cell factor and in the serum levels of the follicle-stimulating hormone. Analysis of mRNA abundance found an increase in cyclins Ccnd3, Ccne1, Ccna2; Kinases Cdk4, Cdk2; and E2F; and Sp1 & Sp3 transcription factors. Decreased expression of cyclin-dependent kinase inhibitor 1a (p21) was observed but not of Cdkn2a inhibitor (p16). The results of the present study identifies, for the first time, the mechanisms associated with biotin supplementation-induced cell proliferation, which raises concerns about the effects of biotin on male reproductive health because of its capacity to cause hyperplasia, especially because this vitamin is available in large amounts without regulation.
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Bal arıları meyve, sebze ve tohum oluşumu için çok önemli hayvanlardır. Arılar, çiçekli bitkilerin erkek yapılarındaki polenleri dişi kısımlarına aktararak bitkilerde meyve ve tohum oluşumunu sağlar. Ayrıca bal yapmaları nedeniyle de tarih boyunca bu böceklere çok önem verilmiştir. Biz insanlar her zaman bal arısına hayran olmuşuzdur. Afrika, Avrupa ve Asya’daki en eski atalarımız, yüz binlerce yıl boyunca, bu arının bal depolama ve balmumu yapma konusundaki şaşırtıcı endüstrisine, çok değerli iki maddeye kesinlikle hayran kaldılar. Daha yakın zamanlarda, son 10.000 yılda, karmaşık arıcılık zanaatını icat ettik ve bal arıları üzerine bilimsel çalışmalarımıza başladık. Örneğin, bu arının «çiçek değişmezliği» uygulamasını ilk kez tanımlayan antik filozof Aristotales’ti: Bir işçi arı, yiyecek toplamanın verimliliğini artırmak için yiyecek arama gezisi boyunca genellikle bir tür çiçeğe yapışır. Bal arısının doğal dünyasında nasıl yaşadığını bilmek, geniş bir bilimsel araştırma yelpazesi gerekmektedir. Bunun nedeni, Apis mellifera’nın biyolojideki, özellikle davranışla ilgili temel soruları araştırmak için model sistemlerden biri haline gelmesidir. Bu arıları ister hayvan bilişindeki, ister davranışsal genetikteki veya sosyal davranışlardaki bazı gizemleri çözmek için çalışıyor olun, birinin deneysel araştırmalarını tasarlamadan önce doğal biyolojilerine aşina olmak kritik derecede önemlidir.
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A concise asymmetric total synthesis of (+)-biotin 1 has been accomplished in which the absolute stereochemistry of C3a, C6a of 1 was established by utilizing an efficient and practical quinine-mediated asymmetric alcoholysis of meso-cyclic anhydride 2 in a single step, the C4 stereochemistry was installed by a direct stereoselective ionic hydrogenation of the thiolactol 7.
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