MitoNEET-Parkin Effects in Pancreatic ?- and ?-Cells, Cellular Survival, and Intrainsular Cross Talk.

ABSTRACT: Mitochondrial metabolism plays an integral role in glucose-stimulated insulin secretion (GSIS) in ?-cells. In addition, the diabetogenic role of glucagon released from ?-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, ?-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 ?-cells leads to fasting-induced hypoglycemia and hypersecretion of insulin during GSIS. MitoNEET-challenged ?-cells exert potent antiapoptotic effects on ?-cells and prevent cellular dysfunction associated with mitoNEET overexpression in ?-cells. These observations identify that reduced mitochondrial function in ?-cells exerts potently protective effects on ?-cells, preserving ?-cell viability and mass.

SUBMITTER: Kusminski CM 

PROVIDER: S-EPMC5310214 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature