Prevention of mitochondrial oxidative damage as a therapeutic strategy in diabetes.
Hyperglycemia causes many of the pathological consequences of both type 1 and type 2 diabetes. Much of this damage is suggested to be a consequence of elevated production of reactive oxygen species by the mitochondrial respiratory chain during hyperglycemia. Mitochondrial radical production associated with hyperglycemia will also disrupt glucose-stimulated insulin secretion by pancreatic beta-cells, because pancreatic beta-cells are particularly susceptible to oxidative damage. Therefore, mitochondrial radical production in response to hyperglycemia contributes to both the progression and pathological complications of diabetes. Consequently, strategies to decrease mitochondrial radical production and oxidative damage may have therapeutic potential. This could be achieved by the use of antioxidants or by decreasing the mitochondrial membrane potential. Here, we outline the background to these strategies and discuss how antioxidants targeted to mitochondria, or selective mitochondrial uncoupling, may be potential therapies for diabetes.
Green
Katherine
K
Medical Research Council Dunn Human Nutrition Unit, Cambridge, UK.
Brand
Martin D
MD
Murphy
Michael P
MP
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D003920:Diabetes Mellitus / Q000188:drug therapy*; D006801:Humans; D008928:Mitochondria / Q000473:pathology*; D018384:Oxidative Stress / Q000502:physiology*; D010101:Oxygen Consumption / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D000975:Antioxidants; D017382:Reactive Oxygen Species; D013481:Superoxides