Is mitochondrial dysfunction a cause of insulin resistance?
Insulin resistance is a key defect associated with obesity and type-2 diabetes. The precise factors that lead to insulin resistance have not been elucidated fully, but there is a strong association between insulin resistance and inappropriate lipid accumulation in insulin-target tissues. Over the past decade, several studies have reported changes in markers of mitochondrial metabolism in insulin-resistant individuals. These observations have led to the theory that compromised mitochondrial oxidative function, particularly in skeletal muscle, causes excess lipid deposition and the development of insulin resistance. Here, we review the latest findings regarding the link between mitochondrial metabolism and insulin action and, in particular, highlight several recent studies that call into question the cause-and-effect relationship between mitochondrial dysfunction and insulin resistance.
Turner
Nigel
N
Diabetes and Obesity Research Program, Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, NSW 2010, Australia. n.turner@garvan.org.au
Heilbronn
Leonie K
LK
D000818:Animals; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D050356:Lipid Metabolism; D008931:Mitochondria, Muscle / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology