Mitochondrial dysfunction in insulin insensitivity: implication of mitochondrial role in type 2 diabetes.
Abundant evidence has been accumulated to suggest that mitochondrial dysfunction is associated with type 2 diabetes. Research findings from this and other laboratories have supported the notion that impaired mitochondrial function is a cause of insulin insensitivity in myocytes and adipocytes as a result of insufficient supply of energy or defects in the insulin signaling pathway. We demonstrated that inhibition of respiration and oxidative phosphorylation by respiratory inhibitors or knockdown of genes involved in mitochondrial biogenesis can impair the differentiation of preadipocytes and response of adipocytes to insulin. Moreover, defective mitochondria also cause a decrease in adiponectin secretion that leads to decline glucose utilization of other tissues. Besides, it has been elucidated that some environmental factors, pollutants, and mitochondrial toxins are involved in the pathogenesis of type 2 diabetes. Taken together, we suggest that mitochondrial dysfunction plays a role in the pathophysiology of insulin insensitivity, and that activation of mitochondrial biogenesis may be an effective strategy in the prevention or treatment of insulin resistance and type 2 diabetes.
Wang
Chih-Hao
CH
Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.
Wang
Ching-Chu
CC
Wei
Yau-Huei
YH
D052242:Adiponectin / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology*; D004785:Environmental Pollutants / Q000633:toxicity; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000209:etiology; D008954:Models, Biological; D009930:Organic Chemicals / Q000633:toxicity; D010085:Oxidative Phosphorylation; D051381:Rats
D052242:Adiponectin; D000975:Antioxidants; D004785:Environmental Pollutants; D007328:Insulin; D015850:Interleukin-6; D009930:Organic Chemicals