MitoNEET-Parkin Effects in Pancreatic alpha- and beta-Cells, Cellular Survival, and Intrainsular Cross Talk

作者：Kusminski Christine M; Chen Shiuhwei; Ye Risheng; Sun Kai; Wang Qiong A; Spurgin Stephen B; Sanders Phillip E; Brozinick Joseph T; Geldenhuys Werner J; Li Wen hong; Unger Roger H; Scherer Philipp E^*

来源：Diabetes, 2016, 65(6): 1534-1555.

DOI：10.2337/db15-1323

Mitochondrial metabolism plays an integral role in glucose stimulated insulin secretion (GSIS) in beta-cells. In addition, the diabetogenic role of glucagon released from alpha-cells plays a major role in the etiology of both type 1 and type 2 diabetes because unopposed hyperglucagonemia is a pertinent contributor to diabetic hyperglycemia. Titrating expression levels of the mitochondrial protein mitoNEET is a powerful approach to fine-tune mitochondrial capacity of cells. Mechanistically, beta-cell specific mitoNEET induction causes hyperglycemia and glucose intolerance due to activation of a Parkin-dependent mitophagic pathway, leading to the formation of vacuoles and uniquely structured mitophagosomes. Induction of mitoNEET in a-cells leads to fasting-induced hypoglycemia and hypersecretion of insulin during GSIS. MitoNEET-challenged alpha-cells exert potent antiapoptotic effects on beta-cells and prevent cellular dysfunction associated with mitoNEET overexpression in beta-cells. These observations identify that reduced mitochondrial function in alpha-cells exerts potently protective effects on beta-cells, preserving beta-cell viability and mass.

• 出版日期2016-6