Figure 7.

A.The expression levels of proteins pathway in JNK signalling in the islet sample from indicated mice. Protein expression was examined by western blotting and normalized to the indicated total protein or GAPDH expression after 4 weeks’ HFD treatment (n = 6 samples per experimental group). B. Total and/or phosphorylated IRS1, AKT, FOXO1, and GAPDH in islet samples of HFD-fed mice that were refed for 4 h after overnight fasting and NC mice under fasting state at the end of 24 weeks. GAPDH serves as the loading control (n = 4 samples per experimental group). All values are means±s.d. Significance determined by two-way analysis of variance with general linear model procedures using a univariate approach. C. C-peptide levels in IKO and Flox mice. D. Schematic illustration of cellular events underlying Miro1-mediated insulin resistance. In response to a continuous challenge with HFD, Miro1 expression is decreased in islet beta cells leading to the activation of mtROS production and mitophagy inhibition, thereby promoting inflammatory response. The activated JNK further aggravates insulin resistance through enhancing IRS phosphorylation at Ser307 and disrupts its downstream AKT-Foxo1 phosphorylation, which contribute to inflammation and insulin resistance, and the resultant T2D.