Mitochondrial Involvement in Skeletal Muscle Insulin Resistance
- Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PA
- Corresponding author: Frederico G.S. Toledo, .
Conflict and mystery are key elements of great suspense stories. Over the last decade, those elements have been present in an intriguing story that has attracted a lot of attention in the field of insulin resistance (IR). The story takes place in a complex scenario: a mix of genetic and acquired abnormalities. The story’s victim is insulin sensitivity in skeletal muscle, but the perpetrators remain fittingly elusive. Suspicions fall on intramyocellular lipid oversupply being the villain. According to prevailing theory, skeletal muscle IR develops as a consequence of excessive lipid content within this tissue. However, it has become increasingly evident that lipid oversupply does not act alone in this story. During the last decade, mitochondria have emerged as an “organelle of interest,” with alleged roles ranging from accomplice to collateral-damage casualty.
A role for mitochondria in IR emerged when studies reported lower mitochondrial oxidative capacity in skeletal muscle of adults with obesity and/or type 2 diabetes (1,2). Other studies concurrently reported lower mitochondrial activity in IR linked to aging and possibly to genetic background in lean individuals with parental history of type 2 diabetes (3–5). Those reports attracted a lot of interest and gave rise to an appealing idea that mitochondrial deficiency may be an important factor in the pathogenesis of IR. According to such a view, a decrease in total mitochondrial oxidative capacity, due to loss in mitochondrial content and/or function, results in insufficient lipid oxidation with the postulated effect being exacerbation of lipid excess and consequent IR.
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