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Experimental Diabetes Research
Volume 2012 (2012), Article ID 703538, 11 pages
Review Article

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

1Division of Experimental Diabetes and Aging, Department of Geriatrics and Palliative Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA
2Division of Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA

Received 20 July 2011; Accepted 3 September 2011

Academic Editor: Sayon Roy

Copyright © 2012 Zhongmin Alex Ma et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Type 2 diabetes mellitus (T2DM) is the most common human endocrine disease and 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 evolution of T2DM. As reviewed elsewhere, reactive oxygen species (ROS) produced by β-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 β-cell failure. ROS activate UCP2, which results in proton leak across the mitochondrial inner membrane, and this leads to reduced β-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 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 developing T2DM. Interventions that attenuate ROS effects on β-cell mitochondrial phospholipids might prevent or retard development of T2DM.