Figure 3.

Simplified scheme that illustrates the role of mitochondrial dysregulation in the pathogenesis of type 2 diabetes in skeletal muscle. Obesity and physical inactivity can result in mitochondrial dysregulation through alterations in crucial transcriptional activators (e.g., PGC-1α and SIRT1), as well as impaired fusion and fission leading to aberrant mitochondrial morphology. These changes can subsequently lead to reduced oxidative capacity and cause lipid metabolite accumulation, increased oxidative stress, and the production of reactive oxygen species (ROS). Over time, the accumulation of ROS can damage DNA, proteins, and lipids, further exacerbating mitochondrial dysfunction. Collectively, these factors contribute to impaired insulin signaling pathways and increase the risk of type 2 diabetes. On the other hand, physiological interventions, including exercise and caloric restriction (CR), as well as pharmacological agents such as thiazolidinediones (TZDs) and resveratrol (RSV) have been shown to stimulate mitochondrial biogenesis and reduce mitochondrial dysfunction that is observed with type 2 diabetes in muscle.