Mitochondrial Dysfunction and Type 2 Diabetes

In this presentation I will review recent studies that address three interrelated topics: 1) the mechanism by which intracellular lipid causes insulin resistance in liver and skeletal muscle; 2) the potential role of mitochondrial dysfunction in promoting increased intracellular lipid accumulation in liver and skeletal muscle in aging and prediabetic states; and 3) the role of skeletal muscle insulin resistance in the pathogenesis of the metabolic syndrome. Abdominal obesity and insulin resistance have each been hypothesized to be the primary factors underlying the metabolic syndrome; however, the biologic mechanisms linking these and other metabolic risk factors associated with the metabolic syndrome are not fully understood and appear to be complex. In this talk, I will examine the hypothesis that insulin resistance in skeletal muscle may promote the development of atherogenic dyslipidemia by diverting ingested carbohydrate away from muscle glycogen storage and into hepatic de novo lipogenesis, resulting in hypertriglyceridemia.