A Defect in Mitochondrial Complex III but Not in Complexes I or IV Causes Early β-Cell Dysfunction and Hyperglycemia in Mice.

Abstract

Mitochondrial metabolism is critical for β-cell insulin secretion, and mitochondrial dysfunction is involved in type 2 diabetes pathogenesis. We determined whether individual oxidative phosphorylation complexes contribute uniquely to β-cell function. Compared with loss of complex I and IV, loss of complex III resulted in severe invivo hyperglycemia and altered β-cell redox status. Loss of complex III altered cytosolic and mitochondrial Ca2+ signaling and increased expression of glycolytic enzymes. Individual complexes contribute differently to β-cell function. This underscores the role of mitochondrial oxidative phosphorylation complex defects in diabetes pathogenesis.