Additionally, chromatin state maps in pancreatic islets were provided and several non-coding RNAs (ncRNA) that are key to T2D pathogenesis were identified (i.e., miR-375).
Up-regulated microRNA-375 is associated with type 2 diabetes and pancreatic islet amyloid formation and beta-cell deficit. microRNA-375 may serve as a biomarker for known and novel pathways in the pathogenesis of type 2 diabetes related to islet amyloid deposition and beta-cell dysfunction.
To explore the clinical significance of seven diabetes-related serum microRNAs (miR-9, miR-29a, miR-30d, miR34a, miR-124a, miR146a and miR375) during the pathogenesis of type 2 diabetes (T2D), 56 subjects were recruited to this study: 18 cases of newly diagnosed T2D (n-T2D) patients, 19 cases of pre-diabetes individuals (impaired glucose tolerance [IGT] and/or impaired fasting glucose [IFG]) and 19 cases of T2D-susceptible individuals with normal glucose tolerance (s-NGT).
It also discusses the regulation of miR-375 expression, miR-375 as a potential circulating biomarker in type 1 and type 2 diabetes, and the need for the beta cell to keep expression of miR-375 within optimal levels.
We verified that miR375 reduced glucose-induced insulin secretion by down-regulating the expression of Mtpn in Nit-1 cells in vitro, suggesting that miR375 has potential therapeutic applications in type II diabetes.
These results suggest that miR-375 and miR-9 are associated with the susceptibility to developing T2D and miR-375 alone or in combination with miR-9 could serve as biomarkers for early detection of prediabetes and T2D.
It was also demonstrated in this study that the miR-375 promoter is hypomethylated, in patients with T2DM, which may regulate the expression of miR-375 and contribute to the pathogenesis of T2DM.
These findings are supported by higher miR-375 levels in the circulation of type 1 diabetes (T1D) subjects but not mature onset diabetes of the young (MODY) and type 2 diabetes (T2D) patients.
The relative expression levels of plasma miR-375 in Kazak T2DM samples are 1, and the relative expression levels of plasma miR-375 in Han T2DM samples are 3.
The relative expression of miR-375 was increased in T2D patients with poor glycaemic control, while a decrease was seen in T2D patients with nephropathy and diabetic foot.