title: Skeletal muscle "mitochondrial deficiency" does not mediate insulin resistance.
abstract: Patients with type 2 diabetes, insulin-resistant obese individuals, and insulin-resistant offspring of patients with diabetes have approximately 30% less mitochondria in their skeletal muscles than age-matched healthy controls. It has been hypothesized that this "deficiency" of mitochondria mediates insulin resistance by impairing the ability of muscle to oxidize fatty acids (FAs). However, a 30% decrease in mitochondria should not impair the ability of muscle to oxidize FAs because the capacity of muscle to oxidize substrate is far in excess of what is needed to supply energy in the basal state, ie, in resting muscle. In pathologic states in which mitochondrial content/function is so severely impaired as to limit substrate oxidation in resting muscle, glucose uptake and insulin action are actually enhanced. Recent studies have shown that feeding rodents high-fat diets and raising FA concentrations results in muscle insulin resistance despite an increase muscle mitochondria that enhances the capacity for fat oxidation. Furthermore, it was recently shown that skeletal muscle mitochondrial capacity for oxidative phosphorylation in Asian Indians with type 2 diabetes is the same as in nondiabetic Indians and higher than in healthy European Americans. In light of this evidence, it seems highly unlikely that "mitochondrial deficiency" causes muscle insulin resistance.
authors.affiliation: Division of Geriatrics and Nutritional Sciences, Washington University School of Medicine, St Louis, MO 63110, USA. jhollosz@dom.wustl.edu
authors.forename: John O
authors.initials: JO
authors.lastname: Holloszy
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D008931:Mitochondria, Muscle / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D010085:Oxidative Phosphorylation
chemical_list: D005227:Fatty Acids