Mitochondria! dysfunction has divergent, cell type-dependent effects on insulin action

The contribution of mitochondria! dysfunction to insulin resistance is a contentious issue in metabolic research. Recent evidence implicates mitochondria! dysfunction as contributing to multiple forms of insulin resistance. However, some models of mitochondria! dysfunction fail to induce insulin resistance, suggesting greater complexity describes mitochondrial regulation of insulin action. We report that mitochondria! dysfunction is not necessary for cellular models of insulin resistance. However, impairment of mitochondria! function is sufficient for insulin resistance in a cell type-dependent manner, with impaired mitochondrial function inducing insulin resistance in adipocytes, but having no effect, or insulin sensitising effects in hepatocytes. The mechanism of mitochondria! impairment was important in determining the impact on insulin action, but was independent of mitochondrial ROS production. These data can account for opposing findings on this issue and highlight the complexity of mitochondrial regulation of cell type-specific insulin action, which is not described by current reductionist paradigms. (C) 2014 The Authors. Published by Elsevier GmbH. Open access under CC BY-NC-ND license