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 profiled during the progression of diabetes after iAs exposure in vivo. In the present study, high iAs (10 mg/L NaAsO2) exposure mice models of C57BKS/Leprdb (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 significant changes in FBG levels in either db/db or WT mice. FBI levels, C-peptide content, and HOMA-IR levels were significantly increased, and glycogen levels in the livers were significantly lower in arsenic-exposed db/db mice. HOMA-β% was decreased significantly 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, pepckand glut4. 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 promising targets to explore the mechanisms and therapeutic aspects of T2DM after exposure to high iAs.