Inhibition of Miro1 disturbs mitophagy and pancreatic β-cell function interfering insulin release via IRS-Akt-Foxo1 in diabetes.

ABSTRACT: Mitochondrial function is essential to meet metabolic demand of pancreatic beta cells respond to high nutrient stress. Mitophagy is an essential component to normal pancreatic β-cell function and has been associated with β-cell failure in Type 2 diabetes (T2D). Our previous studies have indicated that mitochondrial Rho (Miro) GTPase-mediated mitochondrial dysfunction under high nutrient stress leads to NOD-like receptor 3 (NLRP3)-dependent proinflammatory responses and subsequent insulin resistance. However, the in vivo mechanism by which Miro1 underlies mitophagy has not been identified. Here we show firstly that the expression of Miro is reduced in human T2D and mouse db/db islets and in INS-1 cell line exposed to high glucose and palmitate. β-cell specific ablation of Miro1 (Miro

SUBMITTER: Chen L 

PROVIDER: S-EPMC5710878 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature