Skeletal muscle mitochondrial energetics in obesity and type 2 diabetes mellitus: Endocrine aspects

During the development of type 2 diabetes mellitus, skeletal muscle is a major site of insulin resistance. The latter has been linked to mitochondrial dysfunction and impaired fatty acid oxidation. Some hormones like insulin, thyroid hormones and adipokines (e.g., leptin, adiponectin) have positive effects on muscle mitochondrial bioenergetics through their direct or indirect effects on mitochondrial biogenesis, mitochondrial protein expression, mitochondrial enzyme activities and/or AMPK pathway activation - all of which can improve fatty acid oxidation. It is therefore not surprising that treatment with these hormones has been proposed to improve muscle and whole body insulin sensitivity. However, treatment of diabetic patients with leptin and adiponectin has no effect on muscle mitochondrial bioenergetics showing resistance to these hormones during type 2 diabetes. Furthermore, treatment with most thyroid hormones has unexpectedly revealed negative effects on muscle insulin sensitivity. Future research should focus on development of agents tat improve metabolic dysfunction downstream of hormone receptors. (C) 2012 Elsevier Ltd. All rights reserved.