MitoNEET-Parkin effects in pancreatic α-and β-cells, cellular survival, and intrainsular cross talk

CM Kusminski, S Chen, R Ye, K Sun, QA Wang… - Diabetes, 2016 - Am Diabetes Assoc
CM Kusminski, S Chen, R Ye, K Sun, QA Wang, SB Spurgin, PE Sanders, JT Brozinick…
Diabetes, 2016Am Diabetes Assoc
Mitochondrial metabolism plays an integral role in glucose-stimulated insulin secretion
(GSIS) in β-cells. In addition, the diabetogenic role of glucagon released from α-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, β-cell–specific mitoNEET induction causes …
Mitochondrial metabolism plays an integral role in glucose-stimulated insulin secretion (GSIS) in β-cells. In addition, the diabetogenic role of glucagon released from α-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, β-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 α-cells leads to fasting-induced hypoglycemia and hypersecretion of insulin during GSIS. MitoNEET-challenged α-cells exert potent antiapoptotic effects on β-cells and prevent cellular dysfunction associated with mitoNEET overexpression in β-cells. These observations identify that reduced mitochondrial function in α-cells exerts potently protective effects on β-cells, preserving β-cell viability and mass.
Am Diabetes Assoc