Senescence-associated miR-34a and miR-126 in middle-aged Indians with type 2 diabetes

Rapid urbanization and unhealthy dietary patterns critically increase the risk of type 2 diabetes (T2D) in middle-aged Indians. However, despite recent evidence of senescence-associated microRNAs (SA-miRNAs) in regulating complex pathways of ageing, their expressions in middle-aged Indians with T2D remain unexplored. Hence we aimed to investigate the changes in expressions of SA-miRNAs miR-34a and miR-126 in middle-aged T2D patients. A total of 30 T2D patients and 30 controls were recruited of age 31-50 years. The expressions of plasma miR-34a and miR-126 were determined by quantitative PCR. Oxidized LDL (OxLDL) and malondialdehyde (MDA) levels were quantified using enzyme-linked immunosorbent assay (ELISA). The effect of different glucose concentrations on miR-34a, miR-126, senescence-associated, and oxidative stress-responsive genes were also studied in an in vitro model of mice pancreatic beta-cells. MiR-34a was significantly upregulated, whereas miR-126 was nonsignificantly reduced in T2D patients as compared to controls. T2D patients showed elevated levels of oxidative stress markers than controls. Analysis of cultured mice pancreatic beta-cells exposed to high glucose showed significant upregulation of miR-34a, miR-126, p53, and superoxide dismutase 2 (SOD2). We found that circulating miR-34a levels and oxidative stress markers levels were elevated in the middle-aged Indians with T2D as compared to controls. The presence of diabetes may aggravate the normal ageing process in the middle-aged Indians. These SA-miRNAs can also be used to check the cellular dysfunctions and ageing of pancreatic beta-cells.