title: The role of peroxidation of mitochondrial membrane phospholipids in pancreatic β -cell failure.
abstract: Type 2 diabetes (T2D) is characterized by peripheral insulin resistance and pancreatic islet β-cell failure. Accumulating evidence indicates that mitochondrial dysfunction is a central contributor to β-cell failure in the pathogenesis of T2D. This review focuses on mechanisms whereby reactive oxygen species (ROS) produced by β-cell in response to metabolic stress affect mitochondrial structure and function and lead to β-cell failure. Specifically, ROS oxidize mitochondrial membrane phospholipids such as cardiolipin, which impairs membrane integrity and leads to cytochrome c release and apoptosis. In addition, ROS activate UCP2 via peroxidation of the mitochondrial membrane phospholipids, which results in proton leak leading to reduced ATP synthesis and content in β-cells - critical parameters in the regulation of glucose-stimulated insulin secretion. Group VIA Phospholipase A2 (iPLA2β) appears to be a component of a mechanism for repairing mitochondrial phospholipids that contain oxidized fatty acid substituents, and genetic or acquired iPLA2β-deficiency increases β-cell mitochondrial susceptibility to injury from ROS and predisposes to development of T2D. Interventions that attenuate the adverse effects of ROS on β-cell mitochondrial phospholipids may prevent or retard the development of T2D.
authors.affiliation: Division of Experimental Diabetes and Aging, Department of Geriatrics and Palliative Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA. Zhongmin.ma@mssm.edu
authors.forename: Zhongmin A
authors.initials: ZA
authors.lastname: Ma
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D015227:Lipid Peroxidation; D008297:Male; D051336:Mitochondrial Membranes / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D007328:Insulin; D010743:Phospholipids; D017382:Reactive Oxygen Species