Therapeutic potential of lipoamide and enhanced mitochondrial biogenesis for treatment of insulin resistance

Insulin resistance is an important feature of type 2 diabetes (T2D) and obesity. The underlying mechanisms of insulin resistance are still unclear. Mitochondrial dysfunction, including mitochondrial loss and over-production of oxidants, has shown to be involved in the development of insulin resistance and Β-cell dysfunction [1,2]. In prediabetic and diabetic humans, the expression of genes involved in oxidative phosphorylation (OXPHOS) is significantly reduced in the skeletal muscle [3]. Mitochondria are the major sites of reactive oxygen species (ROS) production in the body. If the efficiency of OXPHOS is reduced (e.g., by deletion of energy metabolism genes from the mitochondrial genome), more O₂⁻ is generated at the expense of adenosine triphosphate (ATP). Based on the premise that mitochondrial function is associated with mitochondrial biogenesis, stimulation of mitochondrial biogenesis may have beneficial effects in insulin resistance and T2D. This review summarizes the available evidence-with a focus on our recent studies using lipoamide for stimulating mitochondrial biogenesis-which indicates that this potentially viable strategy for improving mitochondrial function and reducing oxidative stress may lead to prevention and amelioration of T2D.