[Obesity, insulin resistance and skeletal muscle characteristics]

Insulin resistance seems to be a metabolic aberration associated with obesity. Impaired insulin action is also central to a cluster of diseases including non-insulin dependent diabetes, hypertension, dyslipidemias and atherosclerosis. Body fat distribution, especially upper body segment obesity is related to insulin-resistance. Glucose uptake is insulin dependent in skeletal muscle and adipose tissue. From a quantitative standpoint, skeletal muscle has the greater impact on whole body glucose economy, therefore the cause of altered insulin sensitivity has been looked for in this tissue. The skeletal muscle is composed of different types of fibers with specific metabolic and circulatory characteristics; type IIB fibers are less insulin-sensitive and their proportion has been related to obesity and insulin resistance. The different factors that may impair insulin action and alter glucose uptake in skeletal muscle are: lower blood flow to muscle, produced by either decreased vasodilation or by increased sympathetic nerve activity; augmented diffusion distance from capillaries to muscle due to a decrease in capillary number or to enlarged muscle cells; decrease of insulin receptors; change in the fatty acid profile of major membrane structural phospholipids; decrease in glucose transporters (GLUT 4) and/or hexokinase; impairment in metabolic routes of glucose in muscle as reduction in glycogen synthase. Also, the high rate of lipolysis present in obesity and in insulin resistance could lead to an impaired glucose oxidation in muscle.