ABSTRACT
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 signicantly reduced in the skeletal muscle [3]. Mitochondria are the major sites of reactive oxygen species (ROS) production in the body. If the efciency of OXPHOS is reduced (e.g., by deletion of energy metabolism
5.1 Introduction ....................................................................................................93 5.2 Essential Role of Mitochondrial Dysfunction in Insulin Resistance ..............94 5.3 Aberrant Mitochondrial Biogenesis Plays an Important Role in T2D ...........94 5.4 Pathways and Factors Regulating Mitochondrial Biogenesis ......................... 95 5.5 Structure and Biochemical Properties of Lipoic Acid and Lipoamide ..........96 5.6 Transcriptional Activation of Nrf2 and Post-translational Effects of
Lipoic Acid and Lipoamide ............................................................................98 5.7 Actions of Lipoamide in Adipocyte Culture Studies .....................................99 5.8 Potential Therapeutic Role for Lipoamide in Diabetic Polyneuropathies .... 103 5.9 Perspectives .................................................................................................. 104 Acknowledgments .................................................................................................. 105 References .............................................................................................................. 105
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 benecial 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.
