title: Mechanisms of disease: Mitochondrial dysfunction in sensory neuropathy and other complications in diabetes.
abstract: Diabetic neuropathy is a major complication of diabetes that involves the sensory and autonomic nervous systems and leads to significant morbidity and impact on quality of life of patients. Mitochondrial stress has been proposed as a major mediator of insulin sensitivity in skeletal muscle in type 2 diabetes and a trigger of diabetic complications such as nephropathy and cardiomyopathy in humans and animal models. Recent studies in the peripheral nervous system in type 1 and type 2 diabetic animal models suggest a role for mitochondrial dysfunction in neurodegeneration in diabetes. This chapter focuses on the nature of sensory nerve dysfunction in diabetes and presents these findings in the context of diabetes-induced nerve degeneration mediated by alterations in mitochondrial physiology. Diabetes-induced dysfunction in calcium homeostasis is discussed and causative associations with suboptimal mitochondrial physiology are developed. Comparisons are made with mitochondrial-dependent dysfunction in muscle and cardiac tissue in diabetes. It is clear that across a range of complications of diabetes mitochondrial physiology is impaired; in general, a reduction in respiratory chain capability is apparent. Where appropriate, we provide clinical evidence for mitochondrial dysfunction in the pathogenesis of complications in patients with diabetes. This abnormal activity may predispose mitochondria to generate elevated reactive oxygen species (ROS), although experimental proof remains lacking, but more importantly will deleteriously alter the bioenergetic status of neurons.
authors.affiliation: Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Manitoba, Canada; Division of Neurodegenerative Disorders, St Boniface Hospital Research Centre, Winnipeg, Manitoba, Canada. Electronic address: paulfernyhough@yahoo.com.
authors.forename: Paul
authors.initials: P
authors.lastname: Fernyhough
authors.affiliation: Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada; Centre for Physical Activity and Cardiometabolic Health in Youth, Manitoba Institute of Child Health, Winnipeg, Manitoba, Canada.
authors.forename: Jonathan
authors.initials: J
authors.lastname: McGavock
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000378:metabolism; D003920:Diabetes Mellitus / Q000175:diagnosis* / Q000453:epidemiology / Q000378:metabolism; D003929:Diabetic Neuropathies / Q000175:diagnosis* / Q000453:epidemiology / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000175:diagnosis* / Q000453:epidemiology / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology
keywords: Bioenergetics; cardiovascular disease; diabetes; dorsal root ganglia; nerve regeneration; neurodegeneration