Type 2 diabetes patients exhibit subclinical inflammation but the regulatory mechanisms are poorly understood. We sought to evaluate the role of miR-146a expression along with its downstream proinflammatory signals in relation to glycemic control and insulin resistance. Study subjects (n = 20 each) comprised of clinically well characterized Type 2 diabetes patients and control non-diabetic subjects. miRNA and mRNA expression levels were probed in peripheral blood mononuclear cells (PBMC) by Real-time RT-PCR and plasma levels of TNFα and IL-6 were measured by ELISA. The miR-146a expression levels were significantly decreased in PBMCs from patients with Type 2 diabetes compared to control subjects. Among the target genes of miR-146a, TRAF-6 mRNA expression was significantly increased in patients with Type 2 diabetes while there was no significant difference in the mRNA levels of IRAK1 in the study groups. In contrast, there were significantly increased levels of NFκB expression in patients with Type 2 diabetes. There was an increased trend in the levels of TNFα and IL-6 mRNA in patients with type 2 diabetes. While SOCS-3 mRNA levels increased, plasma TNFα and IL-6 levels were also significantly higher in patients with type 2 diabetes. miR-146a expression was negatively correlated to glycated hemoglobin, insulin resistance, TRAF6, and NFκB mRNA levels and circulatory levels of TNFα and IL-6. Reduced miR-146a levels are associated with insulin resistance, poor glycemic control, and several proinflammatory cytokine genes and circulatory levels of TNFα and IL-6 in Asian Indian Type 2 diabetic patients.

Violacein works synergistically with most commercial antibiotics and could be used as drug in combination with other antimicrobial agents.

Although shortened telomeres were shown associated with several risk factors of diabetes, there is lack of data on their relationship with mitochondrial dysfunction. Therefore, we compared the relationship between telomere length and mitochondrial DNA (mtDNA) content in patients with type 2 diabetes mellitus (T2DM; n = 145) and in subjects with normal glucose tolerance (NGT; n = 145). Subjects were randomly recruited from the Chennai Urban Rural Epidemiology Study. mtDNA content and telomere length were assessed by Real-Time PCR. Malonodialdehyde, a marker of lipid peroxidation was measured by thiobarbituric acid reactive substances (TBARS) using fluorescence methodology. Adiponectin levels were measured by radioimmunoassay. Oxidative stress as determined by lipid peroxidation (TBARS) was significantly (p < 0.001) higher in patients with T2DM compared to NGT subjects. In contrast, the mean telomere length, adiponectin and mtDNA content were significantly (p < 0.001) lower in patients with T2DM compared to NGT subjects. Telomere length was positively correlated with adiponectin, HDL, mtDNA content and good glycemic/lipid control and negatively correlated with adiposity and insulin resistance. On regression analysis, shortened telomeres showed significant association with T2DM even after adjusting for waist circumference, insulin resistance, triglyceride, HDL, adiponectin, mtDNA & TBARS. mtDNA depletion showed significant association with T2DM after adjusting for waist circumference and adiponectin but lost its significance when further adjusted for telomere length, TBARS and insulin resistance. Our study emphasizes the clustering of accelerated aging features viz., shortened telomeres, decreased mtDNA content, hypoadiponectinemia, low HDL, and increased oxidative stress in Asian Indian type 2 diabetes patients.

Several omics technologies are underway worldwide with an aim to unravel the pathophysiology of a complex phenotype such as type 2 diabetes mellitus (T2DM). While recent studies imply a clinically relevant and potential biomarker role of circulatory miRNAs in the etiology of T2DM, there is lack of data on this aspect in Indians—an ethnic population characterized to represent ‘Asian Indian phenotype’ known to be more prone to develop T2DM and cardiovascular disease than Europeans. We performed global serum miRNA profiling and the validation of candidate miRNAs by qRT-PCR in a cohort of subjects comprised of normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and patients with T2DM. Our study revealed 4 differentially expressed miRNAs (miR-128, miR-130b-3p, miR-374a-5p, miR-423-5p) in subjects with IGT and T2DM patients compared to control subjects. They were positively or negatively correlated to cholesterol levels, HbA1C, HOMA-IR and fasting insulin. Interestingly, circulating level of miR-128 and miR-130b-3p were also altered in serum of diet-induced diabetic mice compared to control animals. Among the altered circulating miRNAs, miR-128 had never been described in previous studies/populations and appeared to be a ‘New Lead’ in Indians. It was positively correlated with cholesterol both in prediabetic subjects and in diet-induced diabetic mice, suggesting that its increased level might be associated with the development of dyslipedemia associated with T2DM. Our findings imply directionality towards biomarker potential of miRNAs in the prevention/diagnosis/treatment outcomes of diabetes.

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Telomere shortening is emerging as a biological indicator of accelerated aging and aging-related diseases including type 2 diabetes. While telomere length measurements were largely done in white blood cells, there is lack of studies on telomere length in relation to oxidative stress in target tissues affected in diabetes. Therefore, the aim of this study is to induct oxidative stress in adipocytes and to test whether these adipocytes exhibit shortened telomeres, senescence and functional impairment. 3T3-L1 adipocytes were subjected to oxidative stress and senescence induction by a variety of means for 2 weeks (exogenous application of H2O2, glucose oxidase, asymmetric dimethylarginine (ADMA) and glucose oscillations). Cells were probed for reactive oxygen species generation (ROS), DNA damage, mRNA and protein expression of senescent and pro-inflammatory markers, telomere length and glucose uptake. Compared to untreated cells, both ROS generation and DNA damage were significantly higher in cells subjected to oxidative stress and senescence. Adipocytes subjected to oxidative stress also showed shortened telomeres and increased mRNA and protein expression of p53, p21, TNF alpha and IL-6. Senescent cells were also characterized by decreased levels of adiponectin and impaired glucose uptake. Briefly, adipocytes under oxidative stress exhibited increased ROS generation, DNA damage, shortened telomeres and switched to senescent/pro-inflammatory phenotype with impaired glucose uptake.

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