Mitochondrial dysfunction in diabetes: from molecular mechanisms to functional significance and therapeutic opportunities.
Given their essential function in aerobic metabolism, mitochondria are intuitively of interest in regard to the pathophysiology of diabetes. Qualitative, quantitative, and functional perturbations in mitochondria have been identified and affect the cause and complications of diabetes. Moreover, as a consequence of fuel oxidation, mitochondria generate considerable reactive oxygen species (ROS). Evidence is accumulating that these radicals per se are important in the pathophysiology of diabetes and its complications. In this review, we first present basic concepts underlying mitochondrial physiology. We then address mitochondrial function and ROS as related to diabetes. We consider different forms of diabetes and address both insulin secretion and insulin sensitivity. We also address the role of mitochondrial uncoupling and coenzyme Q. Finally, we address the potential for targeting mitochondria in the therapy of diabetes.
Sivitz
William I
WI
Department of Internal Medicine, Division of Endocrinology and Metabolism, Iowa City Veterans Affairs Medical Center and University of Iowa, Iowa City, Iowa, USA. william-sivitz@uiowa.edu
Yorek
Mark A
MA
D000818:Animals; D001786:Blood Glucose / Q000502:physiology; D019069:Cell Respiration / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism; D004579:Electron Transport / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000502:physiology; D007333:Insulin Resistance / Q000502:physiology; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000502:physiology; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000209:etiology / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014451:Ubiquinone / Q000502:physiology
D001786:Blood Glucose; D007328:Insulin; D017382:Reactive Oxygen Species; D013481:Superoxides; D014451:Ubiquinone