Diabetes, oxidative stress, nitric oxide and mitochondria function.
The role of altered mitochondria function has recently emerged as an important mechanism for the development of diabetic complications. Altered mitochondria function has also been implicated in the ageing process, defective insulin secretion, hypertension, arteriosclerosis, ischemia-reperfusion injury and apoptosis. Normally, the mitochondria are associated with ATP production using primarily pyruvate as the substrate, but recent reports indicate that tissue specific preferences exist. Also, the mitochondria are a substantial source of superoxide production, preferentially during states of elevated intracellular glucose concentrations. The mitochondria function is regulated by several factors including nitric oxide, oxidative stress, mammalian target of rapamycin, ADP and P(i) availability, which result in a complex regulation of ATP production and oxygen consumption, but also superoxide generation. These factors seem to be tissue specific, which warrants a more diverse mechanistic model applying to that specific tissue or cell type. This review presents the basic functions of the mitochondria and focuses on the complex interplay between oxidative stress, nitric oxide and uncoupling proteins in regulating mitochondria function with special focus on diabetes-induced alterations occurring on the mitochondria level.
Friederich
Malou
M
Department of Medical Cell Biology, Biomedical Center, Box 571, Uppsala SE-751 23, Sweden. Fredrik.Palm@mcb.uu.se
Hansell
Peter
P
Palm
Fredrik
F
D000255:Adenosine Triphosphate / Q000378:metabolism; D000375:Aging / Q000378:metabolism; D000818:Animals; D003920:Diabetes Mellitus / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D008928:Mitochondria / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*
D007328:Insulin; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D000255:Adenosine Triphosphate