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.
Keywords: β-cell failure, Group VIA phospholipase A2, metabolic stress, mitochondrial phospholipid peroxidation, Reactive Oxygen Species (ROS), repair of mitochondrial membranes, cardiolipin oxidation, Barth Syndrome, monolysocardiolipin acyltransferase, insulin secretion
Current Diabetes Reviews
Title: The Role of Peroxidation of Mitochondrial Membrane Phospholipids in Pancreatic β -Cell Failure
Volume: 8 Issue: 1
Author(s): Zhongmin A. Ma
Affiliation:
Keywords: β-cell failure, Group VIA phospholipase A2, metabolic stress, mitochondrial phospholipid peroxidation, Reactive Oxygen Species (ROS), repair of mitochondrial membranes, cardiolipin oxidation, Barth Syndrome, monolysocardiolipin acyltransferase, insulin secretion
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.
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Cite this article as:
A. Ma Zhongmin, The Role of Peroxidation of Mitochondrial Membrane Phospholipids in Pancreatic β -Cell Failure, Current Diabetes Reviews 2012; 8 (1) . https://dx.doi.org/10.2174/157339912798829232
DOI https://dx.doi.org/10.2174/157339912798829232 |
Print ISSN 1573-3998 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6417 |
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