Search

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 more...

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. more...

Background Diabetes is among the most prevalent diseases worldwide, of all the affected individuals a significant proportion of the population remains undiagnosed due to 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 complication/comorbidities. Methodology The present study utilizes the analytical platform NMR spectroscopy coupled with Random Forest statistical analysis to identify the discriminatory metabolites in diabetes (DB = 38) vs. diabetes-related complication (DC = 35) along with the healthy control (HC = 50) subjects. A combined and pairwise analysis was performed 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). Conclusion The 1H NMR metabolomics may prove a promising technique to differentiate and predict diabetes and its complication on their onset or progression by determining the altered levels of the metabolites in serum. more...

Background: Diabetes is the third widespread after heart disease and cancer. We have investigated genetic polymorphisms in cytokine genes viz. IL-4, IL-1Ra, IL-1β, IL-18, IL-6, TNF-α, IL-10 and ADIPOQ. The aim of study was to investigate the haplotypes, gene-gene interactions and their role in determining individual susceptibility to T2DM of family members with diabetic history. Methods: Haplotype analysis of 2 SNPs each in IL-6 and adiponectin genes showing Pairwise Linkage disequilibrium (LD) was done by SHEsis software. Logistic regression was used to study various combinations of gene-gene interactions. Results: The TCGT* set of allele combination appeared to increase the disease risk upto 2 times while TATG* upto 51.4 times when four SNPs are taken together viz. IL-1β-511 C/T, IL-18-607 A/C, ADIPOQ1 +45 G/T and ADIPOQ2 +10211 T/G. Interaction of SNPs in eight genes showed one highly significant combination of alleles, TCGAGCTT* which increased the risk of T2DM upto 7.4 times while CAGAGCGT* allele combination increased the risk upto 4 times. Conclusion: During pedigree analysis in six families with four SNPs, it was interesting to note that susceptible ‘AC’ genotype of IL-18-607 A/C was frequent in diabetic individuals in almost all families. Moreover, when checked for the presence of risk haplotypes it was observed that TCGT* and TATG* sets of allele combinations were present in most of the diabetic individuals. Individuals with certain abnormal biochemical parameters but not yet diagnosed for T2DM carried the risk genotype or haplotype. This suggested that individuals carrying risk genotypes/haplotypes might be susceptible to T2DM and develop the disease in the future. more...

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. more...

Type 2 diabetes mellitus (T2DM) is a metabolic pro-inflammatory disorder characterized by chronic hyperglycemia and increased levels of circulating cytokines suggesting a causal role of inflammation in its etiology. Polymorphism of cytokine genes including interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and interleukin-10 (IL-10) were studied in T2DM patients as well as in normal healthy controls. Genomic DNA was isolated from both T2DM patients and controls followed by quantification and genotyping by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using suitable primers. The genotypic, allelic and carriage rate frequency distribution in patients and controls were analyzed by SPSS (version 15.0). Odd ratios with 95 % confidence interval was determined to describe the strength of association by logistic regression model. Double and triple combinations of genotypes were analyzed by χ(2) test. Gene-gene interaction and linkage disequilibrium tests were performed using SHEsis software. Individually, IL-6, TNF-α and IL-10 did not show any association. In double combination, IL-6 -597 GA and TNF-α -308 GG genotypes increased the risk up to 21 times and in triple combination IL-6 -597 AA, TNF-α -308 GG and IL-10 -592 CA increased the risk of T2DM up to 314 times. In gene-gene interaction allele 'A' of all studied polymorphisms increased the risk of T2DM up to 1.41 times. Our results suggest that individuals having a haplotype combination of AA, GG and CA for IL-6, TNF-α and IL-10 gene polymorphisms will have higher susceptibility and be at greater risk of developing T2DM. more...

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. more...

Summary Adiponectin (ADIPOQ) is an abundant protein hormone which belongs to a family of so-called adipokines. It is expressed mostly by adipocytes and is an important regulator of lipid and glucose metabolism. It was shown that decreased serum adiponectin concentration indicated insulin resistance and type 2 diabetes (T2DM) with the risk of cardiovascular complications. The fact that adiponectin is an insulin-sensitizing hormone with anti-diabetic, anti-inflammatory and anti-atherogenic properties, we proposed to study the association of ADIPOQ gene polymorphisms in subjects with T2DM. DNA was isolated from venous blood samples, quantified and subjected to Polymerase Chain Reaction–Restriction Fragment Length Polymorphism (PCR–RFLP) using suitable primers and restriction endonucleases. Adiponectin levels were measured in serum using ELISA. The genotypic, allelic and carriage rate frequencies distribution in patients and controls were analyzed by PSAW software (ver. 17.0). Odd ratios (OR) with 95% confidence interval (CI) were determined to describe the strength of association by logistic regression model. Out of the two polymorphisms studied, +10211T/G showed significant association (P = 0.042), the ‘G’ allele association being highly significant (P = 0.022). Further analysis showed that individuals with ‘GG’ haplotype were at increased risk of T2DM up to 15.5 times [P = 0.015, OR (95% CI); 15.558 (1.690–143.174)]. The present study showed that the ‘G’ allele of ADIPOQ gene (+10211T/G) plays a prominent role with respect to T2DM susceptibility in North-Indian population. more...

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. more...

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= more...

Role of Lactic Acid Bacteria as Probiotics in Health and Disease In natural environment a delicate symbiosis evolves between endogenous bacteria and their host is very crucial for maintaining the internal flora of organisms. It stimulates immune system to respond rapidly to infection with pathogens and through bacterial antagonism it inhibits the colonization of the gut by harmful or pathogenic bacteria. A dominant flora represents 90% of the population, essentially composed of Bifidobactrium and Lactobacilli. In group they are called as Lactic Acid Bacteria (LAB) and are collectively called probiotics. These antibacterial effects of LAB are possible due to different antimicrobial compounds like organic acids, hydrogen peroxide (H2O2), carbon dioxide (CO2), fatty acids, reuterin, bacteriocins and other low molecular mass compounds produced by them. Probiotics is playing an important role in prevention of many bacterial diseases also. Probiotic bacteria may add a low-cost, low risk layer of protection from infection and disease. more...

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. more...

Cytokines are small cell signaling protein molecules which encompass a large and diverse family. They consist of immunomodulating agents such as interleukins and inteferons. Virtually all nucleated cells, especially endo/epithelial cells and macrophages are potent producers of IL-1, IL-6 and TNF-α. IL-1 family is a group of cytokines which play a central role in the regulation of immune and inflammatory responses. Type 2 diabetes (T2D) has been recognized as an immune mediated disease leading to impaired insulin signaling and selective destruction of insulin producing β-cells in which cytokines play an important role. Disturbance of anti-inflammatory response could be a critical component of the chronic inflammation resulting in T2D. IL-1 family of cytokines has important roles in endocrinology and in the regulation of responses associated with inflammatory stress. The IL-1 family consists of two pro-inflammatory cytokines, IL-1α and IL-1β, and a naturally occurring anti-inflammatory agent, the IL-1 receptor antagonist (IL-1Ra or IL-1RN). This review is an insight into the different types of cytokines belonging to IL-1 family, their modes of action and association with Type 2 diabetes. more...

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. more...