DOI: 10.21276/sajp.2019.8.6.4

Pages: 299-304

Insulin resistance (IR) is considered to be the primary pathogenesis that introduces Type 2 diabetes mellitus (T2DM) and is often associated with cardiovascular disease including hypertension, dyslipidemia, polycystic ovary syndrome, non-alcoholic fatty liver disease, and certain forms of cancer and sleep apnoea. Insulin resistance (IR), mostly driven by an imbalance between intake and utilization of metabolic substrates such as carbohydrates and lipids persist a prominent hallmark of the metabolic syndrome. Mitochondria are considered to be essential in glucose and lipid metabolism to generate energy in cells. Thus, when nutrient oxidation is inefficient, the ratio of ATP generation/oxygen consumption is low, which leads to an enlarged production of superoxide anions. The formation of reactive oxygen species (ROS) may have maladaptive outcomes which augment the rate of mutagenesis and stimulate proinflammatory processes. In addition to ROS production, decrease in mitochondrial biogenesis, reduced mitochondrial protein content and decrease in activity of the complexes of the electron transport chain (ETC) all contribute to mitochondrial dysfunction. These factors are also responsible to cause insulin resistance in insulin target tissues. Thereby, mitochondrial dysfunction has been involved in the development of IR. Mutually, these observations proposed that mitochondrial dysfunction may be a central organelle which is associated with insulin resistance and associated complications. In this review, we discuss mechanisms of mitochondrial dysfunction associated to the pathophysiology of insulin resistance.