Effects of Inorganic Arsenic on Type 2 Diabetes Mellitus In Vivo: the Roles and Mechanisms of miRNAs

Abstract

Accumulating studies have shown that chronic exposure to iAs correlates with an increased incidence of diabetes. In recent years, miRNA dysfunction has emerged both as a response to iAs exposure and independently as candidate drivers of metabolic phenotypes such as T2DM. However, few miRNAs have been pro led during the progression of diabetes after iAs exposure in vivo. In the present study, high iAs (10 mg/L NaAsO 2 ) exposure mice models of C57BKS/Lepr db (db/db) and C57BLKS/J (WT) were established through the drinking water, the exposure duration was 14 weeks. The results showed that high iAs exposure induced no signi cant changes in FBG levels in either db/db or WT mice. FBI levels, C-peptide content and HOMA-IR levels were signi cantly increased, and glycogen levels in the livers were signi cantly lower in arsenic-exposed db/db mice. HOMA-β% was decreased signi cantly in WT mice exposed to high iAs. In addition, more different metabolites were found in the arsenic-exposed group than the control group in db/db mice, mainly involved in the lipid metabolism pathway. Highly expressed glucose, insulin, and lipid metabolism-related miRNAs were selected, including miR-29a-3p, miR-143-3p, miR-181a-3p, miR-122-3p, miR-22-3p and miR-16-3p. And a series of target genes were chosen for analysis, such as ptp1b, irs1, irs2, sirt1, g6pase, and pepck. The results showed that, the axles of miR-181a-3p-irs2, miR-181a-3p-sirt1, miR-22-3p-sirt1, and miR-122-3p-ptp1b in db/db mice, and miR-22-3p-sirt1, miR-16-3p-glut4 in WT mice could be considered as promising targets to explore the mechanisms and therapeutic aspects of T2DM after exposure to high iAs.

MicroRNAs and Nonalcoholic Steatohepatitis: A Review

“…Diabetes has been identified as an independent risk factor for developing HCC [44]. miRNAs contribute to the onset and progression of type 2 diabetes [45]. miRNAs are involved in the regulation of insulin expression and secretion [46][47][48] Excessive levels of expression of miR-130a, miR-130b, and miR-152 reduce the intracellular ATP/ADP ratio and reduce insulin synthesis and secretion [49].…”