Role In Glucose Tolerance Research Articles

Microbiota and Glucidic Metabolism: A Link with Multiple Aspects and Perspectives.

The global prevalence of overweight and obesity has dramatically increased in the last few decades, with a significant socioeconomic burden. In this narrative review, we include clinical studies aiming to provide the necessary knowledge on the role of the gut microbiota in the development of diabetic pathology and glucose-metabolism-related disorders. In particular, the role of a certain microbial composition of the fermentative type seems to emerge without a specific link to the development in certain subjects of obesity and the chronic inflammation of the adipose tissues, which underlies the pathological development of all the diseases related to glucose metabolism and metabolic syndrome. The gut microbiota plays an important role in glucose tolerance. Conclusion. New knowledge and new information is presented on the development of individualized therapies for patients affected by all the conditions related to reduced glucose tolerance and insulin resistance.

Impact of Vitamin D Elements in Insulin Sensitivity in Type 2 Diabetes Mellitus (DM2)

Numerous non-skeletal diseases have been reported to be associated with vitamin D status including type2diabetes mellitus (T2DM). Different studies provide evidence that vitamin D status as well as other elementssuch as vitamin D binding protein (DBP) and vitamin D receptor (VDR) may play substantial role in glucosetolerance. Present study was designed to investigate the role of vitamin D status and their elements ininsulin resistance or sensitivity in T2DM patients Current study includes 84 participants of both gender(56 patients and 28 as control). Clinical samples were collected from clinically proved DM2 patients.Serum levels of insulin, FBS, VD, VDR, and DBP were measured of each subjects. Using of HomeostasisModel Assessment Insulin resistance (HOMA-IR), T2DM patients were sub grouped to insulin resistance(IR) and insulin sensitivity (IS) groups. Relations among studied factors, FBS showed significant positiveand negative relation with HOMA-IR and VD3 respectively, furthermore HOMA-IR revealed significantpositive relation with DBP and VDR. Also, DBP revealed significant positive relation with each of VDRand HOMA-IR. On the other hand, VD3 levels showed significant and non-significant elevation in IS groupcompared to C and IR group respectively, while DBP revealed significant and non-significant dropping in ISgroup compared to C and IR groups respectively. Levels of VDR in IS group showed significant droppingcompared to C and IR groups respectively. Our study concludes that VD3 alone or with its elements playsubstantial role in regulation of blood sugar levels particularly related to insulin sensitivity

Vitamin D dietary supplementation ameliorates the complications associated with type 2 diabetes induced by streptozotocin

Type 2 diabetes is a major public health problem, accounting for significant premature mortality and morbidity. It has been reported to be associated with several chronic complications which involve coronary artery disease and renal and liver diseases that are considered the primary cause of disability and mortality in diabetic patients. Different studies stated that vitamin D have functional role in glucose tolerance through its effects on insulin secretion and sensitivity and ameliorate type 2 diabetes complication. For that this study was carried out to investigate the effect of dietary vitamin D on type 2 diabetes complication on the liver, pancreas, lipid profile, and brain function. Rats were divided into 5 groups (control, diabetic, Vitamin D treated, Vitamin D preventive, and vitamin D control). Blood and tissue samples were collected after 6 weeks for measurement of fasting blood glucose (FBG), HOMA-IR, fasting serum insulin (FSI), serum lipid profile, blood antioxidants [reduced glutathione (GSH),superoxide dismutase (SOD), and catalase], serum lipid peroxidation product (malondialdehyde (MDA)), and histopathological examination of the pancreas and liver, besides brain acetylcholinesterase (AChE) gene expression. Our results indicated that dietary vitamin D supplementation to diabetic rats significantly increased FSI, decreased FBG and HOMA-IR, enhancing lipid profile by increase HDL-C and decrease LDL-C, TAG, and VLDL-C; Vitamin D also ameliorate GSH level and catalase activity and decrease the level of serum MDA, in addition to depress expression of brain AChE gene and improving liver and pancreas architecture. From these results, it can be concluded that vitamin D assured great protection against type 2 diabetes complications in rats.

Selective slow-wave sleep suppression affects glucose tolerance and melatonin secretion. The role of sleep architecture

ObjectivesOur study aimed to assess the impact of one night of slow-wave sleep (SWS) suppression on glucose tolerance, and explore whether melatonin plays a role in glucose tolerance impairment after SWS suppression. MethodsIn sum, 20 volunteers participated in two experimental sessions: a session with SWS suppression during one night's sleep and a session with a regular night's sleep (control). Each session included collecting seven salivary samples. The following morning, an oral glucose tolerance test (OGTT) was performed. ResultsSWS suppression effects depended on the individual blood glucose response to the OGTT. During the control session, ‘responders’ (N = 11), already presented with low glucose tolerance, which further declined after SWS suppression. ‘Non-responders’ (N = 9) experienced high glucose tolerance in both conditions. Among the responders, SWS suppression led to an increase in melatonin at the moment of awakening, while in non-responders melatonin increased during the first half of the night. In both conditions, responders were characterized by a shorter total sleep time (TST) and less rapid eye movement (REM) sleep. During SWS suppression, they had more non-rapid eye movement (NREM) stage 1 and longer nocturnal wakefulness. Responders and non-responders showed a comparable amount of SWS. ConclusionsThis study highlights three key findings: first, SWS suppression leads to an increase in salivary melatonin; second, melatonin's effect on glucose tolerance depends on its secretion timing; and third, durations of REM sleep and nocturnal awakenings, appear to play an important role in melatonin secretion and glucose tolerance, indicating the potential clinical relevance of these findings for type 2 diabetes risk assessment.

Serum Fetuin-A and Adipsin Levels in Type II Diabetes Patients

Background: Fetuin-A is a glycoprotein known as a biomarker for diabetes risk. Adipsin or complement factor D (CFD) plays a role in glucose tolerance, and metabolism. Objectives: This study aimed to investigate the concentration of fetuin-A and adipsin in patients with type 2 diabetes mellitus (T2DM) and healthy subjects. Patients and Methods: This case–control study was carried out on 43 patients with T2DM and 41 healthy subjects. Biochemical parameters were determined. Fetuin-A and adipsin levels were measured using ELISA kits. Lipid profile and biochemical factors were measured by spectrophotometric methods. Results: The results showed a trend toward lower fetuin-A and CFD concentrations between the two groups (P < 0.05). There was a significant correlation between the levels of fetuin- A and adipsin (P < 0.0001), FBS and HbA1C (P = 0.02), FBS and creatinine (P = 0.03), and BUN (P < 0.001).There was significant differences according to biochemical levels between the two groups (P < 0.001). Conclusions: The findings suggest that fetuin-A and adipsin levels were decreased in T2DM. It seems that the result of fetuin-A and adipsin levels in the diabetes depends on numerous vague factors. Nevertheless, in comparison with published data the changes of fetuin and adipsin levels in patients with T2DM indicate a complex but not complete role of fetuin-A and adipsin in the pathogenesis of T2DM.

Improving the cellobiose-hydrolysis activity and glucose-tolerance of a thermostable β-glucosidase through rational design

β-Glucosidase is the rate-limiting component of a cellulase-hydrolyzing reaction. Thermostability and glucose-tolerance are two critical criteria of the enzyme, which practically determine its performance in industrial applications. In this study, a thermostable and glucose-tolerant β-glucosidase (named Bgl1317) belonging to the glycoside hydrolase family 1 was acquired from a metagenomic library of Turpan soil through functional screening. Bgl1317 showed excellent thermostability and glucose-tolerance and its crystal structure was subsequently determined at a high resolution. Rational design based on the structure was conducted, producing three beneficial mutations A397R, L188A and A262S. While A397R improved the cellobiose activity by 80%, L188A and A262S increased the IC50 value of glucose from 0.8 to 1.5 M. The residues that may play a role in glucose-tolerance of GH1 β-glucosidases were summarized and the performances of glucose-tolerant β-glucosidases reported in recent years were discussed and compared. This study provides insights into enzymatic properties of Bgl1317 for engineering it into a powerful catalyst and β-glucosidases in general.

Significance of Vitamin D on the Susceptibility of Gestational Diabetes Mellitus - A Meta-Analysis.

Vitamin D plays an important role in glucose tolerance by stimulating insulin secretion and evidences suggest a contradictory result on the association between vitamin D status and risk of developing gestational diabetes mellitus (GDM). The present updated meta-analysis has been undertaken to find out the joined effect of vitamin D status on the risk of effect GDM considering previously published articles. Data were collected through literature search using electronic databases to retrieve relevant published research articles using various combinations of the following keywords, “vitamin D,” “vitamin D deficiency,” “cholecalciferol,” “25-hydroxyvitamin D,” “25(OH) D,” “gestational diabetes mellitus,” and “GDM.” A total of 36 studies including 7,596 GDM cases and 23,377 non-GDM controls were involved in this study. Overall, pooled meta-analysis showed that pregnant women diagnosed with GDM have 18% higher risk of GDM risk when compared with controls [odds ratio (OR) = 1.18, 95% confidence interval (CI) 1.10–1.25; P = 0.00] with high heterogeneity (I2 = 73.29). The mean difference was also significantly different between cases and controls (OR = −0.18, 95% CI − 0.22 to − 0.14; P = 0.00). Subgroup analysis showed significant results with age more than 30 years, Asian and European regions, and case–control, cross-sectional, and nested case–control study design. Low concentration of vitamin D is associated with the development of GDM. Although in future more studies especially systematically designed clinical trials based on vitamin D supplementation with large sample size on different population are needed to elucidate the exact concentration of vitamin D during pregnancy as well as before and after pregnancy.

Abstract A38: Twist1-driven fatty pancreas formation facilitates pancreatitis and pancreatic ductal adenocarcinoma progression

Abstract Fatty pancreas or pancreatic steatosis has been associated with a variety of debilitating diseases, such as obesity, diabetes, pancreatitis, and pancreatic ductal adenocarcinoma (PDAC). Currently, neither the mechanisms underlying the pathogenesis of fatty pancreas nor the physiopathologic impacts of this disorder are well established. Serendipitously, we found that conditional overexpression of Twist1 in pancreatic progenitor cells in mice resulted in fatty pancreas development, leading to pancreatic insufficiency, severe hyperglycemia, and growth retardation. Molecular and genetic studies demonstrated that Twist1 drives fatty pancreas formation by selectively reprogramming acinar cells towards the adipocyte lineage albeit without affecting islet or ductal cell fate. Moreover, loss-of-function genetic experiments demonstrated that Twist1 plays a causative role in glucose tolerance, pancreatitis genesis, and PDAC progression. Finally, high levels of Twist1 expression correlate with fatty pancreas formation in patients with pancreatitis or PDAC, implicating Twist1 as a prognostic marker and possible target for attenuating several lethal diseases associated with fatty pancreas development. Citation Format: Thien Ly Nguyen, Purba Singh, Parash Parajuli, Lianna Li, Celine Prunier, Santosh Kumar, Sailaja Eragmerdi, Seval Ozkan, Hao Me, Jussara do Carmo, John Hall, Azeddine Atfi. Twist1-driven fatty pancreas formation facilitates pancreatitis and pancreatic ductal adenocarcinoma progression [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr A38.

Investigation of Blood Betatrophin Levels in Obese Children with Non-Alcoholic Fatty Liver Disease.

PurposeThe prevalence of obesity has significantly increased among children and adolescents worldwide and is becoming an important health care problem in parallel with the increased prevalence of obesity pediatric non-alcoholic fatty liver disease. Betatrophin is a newly define hormone that is commonly secreted by liver and plays role in glucose tolerance. This study aimed to investigate the relationship between serum betatrophin levels and non-alcoholic fatty liver disease in obese children.MethodsThe study included 40 obese children with a body mass index (BMI) above 95th centile, and 35 non-obese subjects with a BMI 3-85th centile, whose age and gender were similar to those of the patient group. For the evaluation of metabolic parameters fasting serum glucose, insulin, alanine aminotransferase, aspartate aminotransferase, lipid profile and serum betatrophin levels were measured. Total cholesterol: high-density lipoprotein cholesterol and low-density lipoprotein cholesterol: high-density lipoprotein cholesterol ratios were calculated as “atherogenic indices.”ResultsSerum betatrophin levels of the obese subjects were similar to that of non-obese subjects (p=0.90). Betatrophin levels were not correlated with the metabolic parameters.ConclusionIn the present study, levels of betatrophin are not different between obese and insulin resistant children and non-obese subjects, and they are not correlated with atherogenic indices. To elucidate the exact role of betatrophin in obesity, further studies are required to identify the betatrophin receptor and/or other possible cofactors.

Gender Specific Association of Serum Leptin and Insulinemic Indices with Nonalcoholic Fatty Liver Disease in Prediabetic Subjects.

Adipose tissue-derived hormone leptin plays a functional role in glucose tolerance through its effects on insulin secretion and insulin sensitivity which also represent the risk factors for nonalcoholic fatty liver disease (NAFLD). The present study explored the gender specific association of serum leptin and insulinemic indices with NAFLD in Bangladeshi prediabetic subjects. Under a cross-sectional analytical design a total of 110 ultrasound examined prediabetic subjects, aged 25–68 years consisting of 57.3% male (55.6% non NAFLD and 44.4% NAFLD) and 42.7% female (57.4% non NAFLD and 42.6% NAFLD), were investigated. Insulin secretory function (HOMA%B) and insulin sensitivity (HOMA%S) were calculated from homeostasis model assessment (HOMA). Serum leptin showed significant positive correlation with fasting insulin (r = 0.530, P = 0.004), postprandial insulin (r = 0.384, P = 0.042) and HOMA-IR (r = 0.541, P = 0.003) as well as significant negative correlation with HOMA%S (r = -0.388, P = 0.046) and HOMA%B (r = -0.356, P = 0.039) in male prediabetic subjects with NAFLD. In multiple linear regression analysis, log transformed leptin showed significant positive association with HOMA-IR (β = 0.706, P <0.001) after adjusting the effects of body mass index (BMI), triglyceride (TG) and HOMA%B in male subjects with NAFLD. In binary logistic regression analysis, only log leptin [OR 1.29 95% (C.I) (1.11–1.51), P = 0.001] in male subjects as well as HOMA%B [OR 0.94 95% (C.I) (0.89–0.98), P = 0.012], HOMA-IR [OR 3.30 95% (C.I) (0.99–10.95), P = 0.049] and log leptin [OR 1.10 95% (C.I) (1.01–1.20), P = 0.026] in female subjects were found to be independent determinants of NAFLD after adjusting the BMI and TG. Serum leptin seems to have an association with NAFLD both in male and female prediabetic subjects and this association in turn, is mediated by insulin secretory dysfunction and insulin resistance among these subjects.

Association of serum copper level with fasting serum glucose in south Indian women with gestational diabetes mellitus

Background and Aim: Prevalence of gestational diabetes mellitus (GDM) is higher in southern region compared to other parts of India. Deficiency of certain trace elements has been indicated in the progression of type 2 diabetes mellitus. Therefore, an inadequate supply of micronutrients in pregnancy may compromise the health and growth of both mother and fetus. Though copper and magnesium have an important role in glucose tolerance, they are not routinely checked in pregnancy. Therefore, this study was designed to determine the serum level of copper and magnesium in GDM patients and compare it with that of euglycemic pregnant women with similar gestational age. Methods: Serum was collected at 0, 1 st and 2 nd h from the blood drawn from pregnant ladies as part of their screening test for oral glucose tolerance test (OGTT), after obtaining informed consent. Serum copper and magnesium was estimated from fasting serum sample. Results: This prospective study showed a significant increase in copper level without significant change in magnesium level in GDM patients compared with euglycemic pregnant women. The increase in serum copper level was positively correlated with the rise in fasting serum glucose. Linear regression demonstrated association of serum copper level to fasting blood glucose (beta = 0.265, P = 0.017). Conclusion: Rise in serum copper level in GDM is linked to the level of fasting blood glucose. Therefore, women, who are diagnosed with GDM and found to have higher copper level, should be monitored carefully for ill-effects of higher copper level as it is linked to their hyperglycemic status.

The effect of vitamin D on insulin resistance in patients with type 2 diabetes.

IntroductionOver the past decade, numerous non-skeletal diseases have been reported to be associated with vitamin D deficiency including type2 diabetes mellitus (T2DM). Different studies provide evidence that vitamin D may play a functional role in glucose tolerance through its effects on insulin secretion and insulin sensitivity. This study evaluates the effects of vitamin D supplementation on insulin resistance in T2DM.MethodThrough a before-after study, 100 patients with T2DM, 30–70 years old, were recruited from an Arak diabetes clinic as consecutive attenders. Participants were assessed for clinical and biochemistry. Serum insulin and, 25(OH)D concentration, and HOMA-IR was calculated. All measurements were performed at the beginning and the end of the study. Patients received 50,000 unit of vitamin D3 orally per week for eight weeks, Statistical analysis was made using SPSS17. The results were analyzed by descriptive tests, and a comparison between variables were made using paired T-tests or Wilcoxon tests, as appropriate.Results100 participants including 70 women (70%) and 30 men (30%) took part in the study. All results were presented as Mean±SD, or medians of non-normally distributed.24% of the participants were Vitamin D deficient {serum 25(OH)D ≤ 20 ng/ml(50 nmol/l)}.Mean serum 25 (OH) D concentration was 43.03± 19.28 ng/ml (107.5±48.2 nmol/l).The results at baseline and at the end, for FPG were 138.48±36.74 and 131.02±39 mg/dl (P=0.05), for insulin, 10.76±9.46 and 8.6±8.25 μIu/ml (P=0.028) and for HOMA-IR, 3.57±3.18 and 2.89±3.28 (P=0.008) respectively.ConclusionOur data showed significant improvements in serum FPG, insulin and in HOMA-IR after treatment with vitamin D, suggested that vitamin D supplementation could reduce insulin resistance in T2DM.

Role of Adipokines and Other Inflammatory Mediators in Gestational Diabetes Mellitus and Previous Gestational Diabetes Mellitus

Previous Gestational Diabetes Mellitus (pGDM) is a common condition and has been associated with future development of Type 2 Diabetes Mellitus (T2DM) and Metabolic Syndrome (MS) in women affected. The pathogenesis and risk factors implicated in the development of these conditions later in the lives of women with pGDM are not as yet fully understood. Research has recently focused on a group of substances produced mainly by adipose tissue called adipokines, this group including, among others, adiponectin, leptin, Retinol-Binding Protein-4 (RBP-4), and resistin. These substances as well as other inflammatory mediators (CRP, IL-6, PAI-1, TNF-α) seem to play an important role in glucose tolerance and insulin sensitivity dysregulation in women with pGDM. We summarize the data available on the role of these molecules.

H. pylori's Role in Glucose Tolerance Under Investigation

H. pylori's Role in Glucose Tolerance Under Investigation

The 184th residue of β-glucosidase Bgl1B plays an important role in glucose tolerance

Bgl1B (ACY09072) is a new GH1 family β-glucosidase derived from a marine microbial metagenomic library. In our previous study, the activity of recombinant Bgl1B was competitively inhibited by glucose with an IC₅₀ value of 30 mM. Based on amino acids sequence alignment with other GH1 β-glucosidases, including BglB from Paenibacillus polymyxa whose structure has been solved, the 184th and 409th residues of Bgl1B were suggested to be key residues relating to glucose tolerance or other properties. The putative role of the two residues of Bgl1B was investigated by site-directed mutagenesis by replacing His184 and Leu409 with Phe and Glu, respectively. Biochemical characterization data indicated that the mutations had little influence on the enzyme properties. However, in comparison with wild-type Bgl1B, the mutant H184F exhibited lower stability at all tested temperatures and pHs, while L409E exhibited higher stability. Particularly, when using 4-Nitrophenyl-β-D-glucopyranoside (pNPG) as substrate, the mutant H184F exhibited much better glucose tolerance, with a K(i) of 76.9 mM, than L409E and wild-type Bgl1B (17.2 mM and 14.9 mM, respectively). These results indicated that the 184th residue might play an important role in the glucose tolerance of Bgl1B.

Effects of fructose on hepatic glucose metabolism.

The liver plays an important role in glucose tolerance. A number of studies have suggested fructose improves glucose tolerance especially in insulin resistant settings. This review summarizes the recent work suggesting that fructose enhances glucose tolerance by augmenting liver glucose uptake. This increase may be mediated by the translocation and activation of hepatic glucokinase. Catalytic quantities of fructose (<10% of total carbohydrate flux) enhance liver glucose uptake in a dose dependent manner. The primary fate of the glucose is glycogen synthesis. The ability of fructose to augment liver glucose uptake is not impaired by the presence of marked insulin resistance such as in type 2 diabetes or infection. In addition, it is able to further enhance liver glucose uptake in the normal adapted setting of total parenteral nutrition and reverse the infected-induced decrease in liver glucose uptake. Studies also demonstrate that the beneficial effects of fructose on liver glucose uptake during chronic nutritional support do not persist. Fructose is a potent acute regulator of liver glucose uptake and glycogen synthesis. Inclusion of catalytic quantities of fructose in a carbohydrate meal improves glucose tolerance. This improvement is primarily mediated by the activation of hepatic glucokinase and consequent facilitation of liver glucose uptake. The improvement in glucose tolerance is most evident in insulin resistant settings (e.g. Type 2 diabetes and infection). The beneficial effect of fructose on hepatic glucose disposal, however, does not persist if fructose is given continuously such as in total parenteral nutrition.