"Deficiency" of mitochondria in muscle does not cause insulin resistance

Diabetes. 2013 Apr;62(4):1036-40. doi: 10.2337/db12-1107.

Abstract

Based on evidence that patients with type 2 diabetes (T2DM), obese insulin-resistant individuals, and lean insulin-resistant offspring of parents with T2DM have ~30% less mitochondria in their muscles than lean control subjects, it appears to be widely accepted that mitochondrial "deficiency" is responsible for insulin resistance. The proposed mechanism for this effect is an impaired ability to oxidize fat, resulting in lipid accumulation in muscle. The purpose of this counterpoint article is to review the evidence against the mitochondrial deficiency concept. This evidence includes the findings that 1) development of insulin resistance in laboratory rodents fed high-fat diets occurs despite a concomitant increase in muscle mitochondria; 2) mitochondrial deficiency severe enough to impair fat oxidation in resting muscle causes an increase, not a decrease, in insulin action; and 3) most of the studies comparing fat oxidation in insulin-sensitive and insulin-resistant individuals have shown that fat oxidation is higher in T2DM patients and obese insulin-resistant individuals than in insulin-sensitive control subjects. In conclusion, it seems clear, based on this evidence, that the 30% reduction in muscle content of mitochondria in patients with T2DM is not responsible for insulin resistance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism
  • Animals
  • Diabetes Mellitus, Type 2 / metabolism
  • Energy Metabolism
  • Humans
  • Insulin Resistance / physiology*
  • Mitochondria, Muscle / metabolism*
  • Muscle, Skeletal / metabolism*
  • Obesity / metabolism
  • Oxidation-Reduction