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Adipocytes secreate many adipocytokines including visfatin. Many evidence either in direct relation or in in vitro showed that visfatin alters the state of type 2 diabetes (T2DM).To unfold the role of visfatin in response to metformin and pioglitazone we have investigated the lipid profile and levels of visfatin along with its mRNA expression in response to antidiabetic drugs metformin and pioglitazone in vitro adipocytes.Adipocytes were cultured for the estimation of lipid profile and secreted visfatin using ELISA and the response of mRNA visfatin gene expression by the use of metformin hydrochloride and pioglitazone hydrochloride and combination of both.The determination was performed by RT- PCR quantification. Differences were considered significant when P values were ≤0.05 calculated using SPSS software (ver. 19).In Glucose treated adipocytes the lipid profile showed significant change in HDL while highly significant change in other lipoproteins.However,the released level of visfatin also showed significant change in glucose treated adipocytes as compared to normal control adipocytes. No significant change was observed in metformin hydrochloride while pioglitazone hydrochloride showed significant change as concurred by mRNA level estimation. The present report examined whether visfatin is regulated by anti-diabetic drugs metformin and pioglitazone in glucose feed adipocytes mimicking the state of T2DM along with effect of these drugs in secreted lipid profile. Pioglitazone treatment showed highly significant association at higher concentration. Our finding suggest that the treatment with pioglitazone in glucose treated adipocytes could play a role in the regulation of visfatin in adipocytes

Background Diabetes especially type 2 diabetes mellitus (T2DM) is securing the rank under five around the world and leading cause of death cardiac disease and cancer. T2DM is a severe inflammatory state mainly associated to obesity and enhanced oxidative stress. Objectives We have investigated eleven genetic polymorphisms of seven important genes viz. IL-10, TNF-α, IL-6, adiponectin, IL-1, IL-18, and Vitamin D-receptor. We have focused to investigate the haplotypes, gene-gene interactions and their role in determining individual susceptibility to T2DM and their manifestation. Methods Eleven genetic variants of seven important candidate genes in 440 T2DM individuals and 440 controls were genotyped using conventional polymerase chain reaction (PCR) and PCR restriction fragment length polymorphism (PCR-RFLP). All calculations were done by SPSS software and LD were analysed by haploview (SHEsis software). Results Genotypic frequency of rs1800872, rs1800795, rs2241766, rs17846866 and rs1946518 showed highly significant association in our population. While allele frequencies of rs1800795, rs2241766 and rs1946518 showed highly significant association. The allele set of “CGGAGGTAFTB”, “CGGAGTTAFTB” and “CGGATGTCFTB” increase the chance of diabetes up to 1.6 times. This study reflects that these individuals are more susceptible of having T2DM. Conclusions The present study will provide a new insight in the development and the manifestation of T2DM. These genetic studies showing gene interaction for the susceptibility of the disease may be used as prognostic markers and alter treatment strategies for T2DM.

Introduction TNF-α, a proinflammatory cytokine secreted by activated immune cells, and overexpression of it in adipocytes, has an important role in insulin resistance progression and diabetes development. Aim and objective Subcutaneous adipocytes derived from mesenchymal stem cells were used for in vitro analysis to find the role of antidiabetic drugs on TNF-α in high glucose-fed adipocytes. Methods In vitro adipocytes were used along with variable concentration of anti-diabetic drugs. The level of TNF-α was measured by ELISA and the mRNA level was quantified using SYBR-Green real-time PCR. All data were statistically analyzed. Results The level of TNF-α and the mRNA expression were observed and analyzed with normal adipocytes. TNF-α level and expression of it showed agonistic behavior, ie no change at low concentration while enhances with the increase of glucose. The level was decreased significantly when the adipocytes were treated with metformin (p=0.015) and pioglitazone (p=0.020). A combination of drugs showed that the expression of TNF-α was almost the same as for metformin alone. However, insulin increases the TNF-α expression as for pioglitazone. Discussion Such a report on adipocytes may be helpful for clinical benefits to understand the additional mechanism of adipocytes on the release and expression of TNF-α. However, anti-diabetic drugs including insulin up-regulate the TNF-α gene expression in mild or severe glucose load.

To date, there is no satisfactory and effective therapy available to cure type 2 diabetes mellitus (T2DM). This present work is focused on plant extracts and the effect of saroglitazar and TET genes on oxidative stress and inflammation in vitro adipocytes. Aqueous extracts of

To date, there is no satisfactory and effective therapy available to cure type 2 diabetes mellitus (T2DM). This present work is focused on plant extracts and the effect of saroglitazar and TET genes on oxidative stress and inflammation in vitro adipocytes. Aqueous extracts of Tamarindus indica and Momordica charantia seed have shown potent antidiabetic activity that decreases glucose levels in diabetic adipocytes. After seven and fourteen days, the sugar level in the blood was significantly reduced when plant extracts were supplemented. Lipid profiles including total cholesterol (TC), triglyceride (TGL), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) showed a highly significant change as expected in adipocytes treated with glucose compared with controlled adipocytes ( P < 0.001 ). Gene expression of catalase, superoxide dismutase (SOD1, SOD2), and glutathione peroxidase (GPx) are changed twice, thrice, and quadruplet, respectively. The level of interleukin-1 (IL1) and tumor necrosis factor-α (TNF-α) was restored but the interleukin-6 (IL6) and ten-eleven-translocation-1 (TET1) were completely knocked down by the use of saroglitazar. In comparison with the diabetic group, this supplementation significantly increased glycogen content and glucose-6-phosphate dehydrogenase activity. In the extract supplemented group, glucose-6-phosphatase, glucose-oxidizing enzyme, and glucose-phosphorylating enzyme activities were significantly reduced. After seven days of extract supplementation, these parameters were not resettled to a controlled level; however, after 14 days of supplementation, all parameters were restored to the control level. In addition to altering gene expression, TET enzymes may contribute to altered adiposity and its metabolic consequences. The purpose of this study is to examine new ideas and approaches for treating obesity, T2DM, and other associated metabolic disorders.

Introduction TNF-α, a proinflammatory cytokine secreted by activated immune cells, and overexpression of it in adipocytes, has an important role in insulin resistance progression and diabetes development. Aim and Objective Subcutaneous adipocytes derived from mesenchymal stem cells were used for in vitro analysis to find the role of antidiabetic drugs on TNF-α in high glucose-fed adipocytes. Methods In vitro adipocytes were used along with variable concentration of anti-diabetic drugs. The level of TNF-α was measured by ELISA and the mRNA level was quantified using SYBR-Green real-time PCR. All data were statistically analyzed. Results The level of TNF-α and the mRNA expression were observed and analyzed with normal adipocytes. TNF-α level and expression of it showed agonistic behavior, ie no change at low concentration while enhances with the increase of glucose. The level was decreased significantly when the adipocytes were treated with metformin (p=0.015) and pioglitazone (p=0.020). A combination of drugs showed that the expression of TNF-α was almost the same as for metformin alone. However, insulin increases the TNF-α expression as for pioglitazone. Discussion Such a report on adipocytes may be helpful for clinical benefits to understand the additional mechanism of adipocytes on the release and expression of TNF-α. However, anti-diabetic drugs including insulin up-regulate the TNF-α gene expression in mild or severe glucose load.

Background: Diabetes is among the most prevalent diseases worldwide, of all the affected individuals a significant proportion of the population remains undiagnosed because of a lack of specific symptoms early in this disorder and inadequate diagnostics. Diabetes and its associated sequela, i.e., comorbidity are associated with microvascular and macrovascular complications. As diabetes is characterized by an altered metabolism of key metabolites and regulatory pathways. Metabolic phenotyping can provide us with a better understanding of the unique set of regulatory perturbations that predispose to diabetes and its associated comorbidities. Methodology: The present study utilizes the analytical platform NMR spectroscopy coupled with Random Forest statistical analysis to identify the discriminatory metabolites of diabetes (DB) and diabetes-related comorbidity (DC) along with the healthy control (HC) subjects. A combined and pairwise analysis was performed, between the serum samples of HC (n=50), and DB (n=38), and DC (n=35) individuals to identify the discriminatory metabolites responsible for class separation. The perturbed metabolites were further rigorously validated using t-test, AUROC analysis to examine the statistical significance of the identified metabolites. Results: The DB and DC patients were well discriminated from HC. However, 15 metabolites were found to be significantly perturbed in DC patients compared to DB, the identified panel of metabolites are TCA cycle (succinate, citrate), methylamine metabolism (trimethylamine, methylamine, betaine), -intermediates; energy metabolites (glucose, lactate, pyruvate); and amino acids (valine, arginine, glutamate, methionine, proline and threonine). The metabolites were further used to identify the perturbed metabolic pathway and correlation of metabolites in DC patients. Conclusion: The 1H NMR metabolomics may prove a promising technique to differentiate and predict diabetes and its comorbidities on their onset or progression by determining the altered levels of the metabolites in serum.

Indians undergoing socioeconomic and lifestyle transitions will be maximally affected by epidemic of type 2 diabetes (T2D). We conducted a two-stage genome-wide association study of T2D in 12,535 Indians, a less explored but high-risk group. We identified a new type 2 diabetes–associated locus at 2q21, with the lead signal being rs6723108 (odds ratio 1.31; P = 3.32 × 10−9). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 × 10−12) within TMEM163 that encodes a probable vesicular transporter in nerve terminals. TMEM163 variants also showed association with decreased fasting plasma insulin and homeostatic model assessment of insulin resistance, indicating a plausible effect through impaired insulin secretion. The 2q21 region also harbors RAB3GAP1 and ACMSD; those are involved in neurologic disorders. Forty-nine of 56 previously reported signals showed consistency in direction with similar effect sizes in Indians and previous studies, and 25 of them were also associated (P < 0.05). Known loci and the newly identified 2q21 locus altogether explained 7.65% variance in the risk of T2D in Indians. Our study suggests that common susceptibility variants for T2D are largely the same across populations, but also reveals a population-specific locus and provides further insights into genetic architecture and etiology of T2D.

In this first report on the association of an IL-10 promoter polymorphism with type 2 diabetes mellitus in a North Indian population, the −592A/C SNP (rs1800872) was genotyped by PCR–RFLP and the IL-10 level measured using ELISA. Although no significant difference was observed in the genotypic frequencies (P = 0.657), diabetes patients carried a significantly higher number of A alleles at the −592 position, 25.6% (P < 0.001, odds ratio 0.887, 95% CI 0.670–1.184). Significant correlations were detected in postprandial glucose levels of CC-genotype patients and controls (P = 0.025), age and waist–hip ratio of CA patients and controls (P ≤ 0.001), and fasting glucose (P = 0.045) and low-density lipoprotein (P = 0.049) in all patients and controls. The serum IL-10 level was significantly higher in patients than in controls (P = 0.033). The polymorphism was significantly associated with disease incidence and its biochemical manifestations.

IntroductionType 2 diabetes mellitus (T2DM) affects huge populations in India and abroad. Genetic polymorphisms (SNPs) in scavenger receptors such as CD36 have been implicated in the pathogenesis of diabetic atherosclerosis and cardiovascular diseases. Since CD36 gene expression contributes to T2DM, we proposed to study the association of two of its polymorphisms.MethodsA population of 400 subjects from North India was analyzed according to clinical parameters. Out of them 150 controls and 250 T2DM patients were genotyped for two SNPs namely rs1761667 (G>A) and rs1527483 (C>T) in the CD36 gene using polymerase chain reaction and restriction fragment length polymorphism (PCR–RFLP) followed by statistical analysis.Results and discussionNo association of rs1527483 (C>T) SNP was observed in T2DM patients. The GA genotype was prevalent in 76.0% diabetic population and a highly significant genotypic association of rs1761667 (G>A) SNP in CD36 gene was observed in them (P=

An effort has been made in this review to outline the origin of diabetes as a serious disease. A large number of studies are going on in order to understand the cause of this disease, both environmental as well as genetic factors have been found to be involved. We have tried to throw some light on inflammation in diabetes with special emphasis on interleukins and adipocytokines. Recently the involvements of cytokines and adipocytokines have been extensively studied and have been found to play an extremely important role in the manifestation of diabetes and its associated complications.

Diabetes mellitus is a combined metabolic disorder which includes hyperglycemia, dyslipidemia, stroke and several other complications. Various groups all over the world are relentlessly working out the possible role of a vast number of genes associated with type 2 diabetes (T2DM). Inflammation is an important outcome of any kind of imbalance in the body and is therefore an indicator of several diseases, including T2DM. Various ethnic populations around the world show different levels of variations in single nucleotide polymorphisms (SNPs). The present review was undertaken to explore the association of cytokine gene polymorphisms with T2DM in populations of different ethnicities. This will lead to the understanding of the role of cytokine genes in T2DM risk and development. Association studies of genotypes of SNPs present in cytokine genes will help to identify risk haplotype(s) for disease susceptibility by developing prognostic markers and alter treatment strategies for T2DM and related complications. This will enable individuals at risk to take prior precautionary measures and avoid or delay the onset of the disease. Future challenges will be to understand the genotypic interactions between SNPs in one cytokine gene or several genes at different loci and study their association with T2DM.

Background : The vitamin D receptor (VDR) gene is a candidate gene for susceptibility to several diseases. Studies on association between VDR polymorphisms and risk of type 2 diabetes (T2DM) in different ethnic populations are yet inconclusive. Aims : This study was conducted to evaluate association between VDR polymorphisms and genetic susceptibility to T2DM in the north Indian population. Settings and Design : One hundred clinically diagnosed T2DM patients and 160 healthy controls from the north Indian population were recruited for genetic association study. Materials and Methods : Genomic DNA was extracted from blood and genotyped for the single nucleotide polymorphism SNPs of FokI (T/C) [rs2228570], BsmI (A/G) [rs1544410] and TaqI (C/T) [rs731236] by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. Statistical Analysis Used : Genotype distribution and allelic frequencies were compared between patients and controls. Mean values and odds ratios (ORs) with 95% confidence interval (CI) were calculated using SPSS software (version 15.0). Results : The genotype distribution, allele and haplotype frequencies of VDR polymorphism did not differ significantly between patients and controls. Mean age and waist-hip ratio of patients were found to be associated with VDR polymorphism. Combination studies showed FFBbtt increased the risk of T2DM in north Indians. Conclusions : Our data suggest that VDR gene polymorphism in combination of genotypes is associated with the risk of T2DM and thus requires further studies as a probable genetic risk marker for T2DM.