Mitochondrial Dysfunction and beta-Cell Failure in Type 2 Diabetes Mellitus

作者：Ma Zhongmin Alex^*; Zhao Zhengshan; Turk John

来源：Experimental Diabetes Research, 2012, 2012: 703538.

DOI：10.1155/2012/703538

Type 2 diabetes mellitus (T2DM) is the most common human endocrine disease and is characterized by peripheral insulin resistance and pancreatic islet beta-cell failure. Accumulating evidence indicates that mitochondrial dysfunction is a central contributor to beta-cell failure in the evolution of T2DM. As reviewed elsewhere, reactive oxygen species (ROS) produced by beta-cell mitochondria as a result of metabolic stress activate several stress-response pathways. This paper focuses on mechanisms whereby ROS affect mitochondrial structure and function and lead to beta-cell failure. ROS activate UCP2, which results in proton leak across the mitochondrial inner membrane, and this leads to reduced beta-cell ATP synthesis and content, which is a critical parameter in regulating glucose-stimulated insulin secretion. In addition, ROS oxidize polyunsaturated fatty acids in mitochondrial cardiolipin and other phospholipids, and this impairs membrane integrity and leads to cytochrome c release into cytosol and apoptosis. Group VIA phospholipase A(2) (iPLA(2)beta) appears to be a component of a mechanism for repairing mitochondrial phospholipids that contain oxidized fatty acid substituents, and genetic or acquired iPLA(2)beta-deficiency increases beta-cell mitochondrial susceptibility to injury from ROS and predisposes to developing T2DM. Interventions that attenuate ROS effects on beta-cell mitochondrial phospholipids might prevent or retard development of T2DM.

• 出版日期2012