Vnitr Lek 2003, 49(12):894-899

[Pathogenesis of insulin resistance].

J Skrha: III. interní klinika 1. lékarské fakulty UK a VFN, Praha.

Insulin resistance characterized by a decreased biological response to insulin is caused by genetic and exogenous factors influencing the target tissues for insulin, like the muscle, adipose tissue and the liver. A hyperbolic relationship was found between insulin secretion and insulin action. The insulin hypersecretion caused by short-time B-cell stimulation with free fatty acids is associated with hyperinsulinemia and worsening of insulin resistance. On the contrary, longtime exposure of B-cells by free fatty acids is followed by a decreased secretion and thus by hypoinsulinemia. Triglyceride infiltration of the muscle tissue and B-cells further worsens the insulin resistance and impairs the insulin secretion. Lipotoxicity worsens the whole metabolic disorder including the glucose tolerance and causes apoptosis of the islet cells. Free fatty acids are causative factor in the pathogenesis of insulin resistance as well as of Type 2 diabetes.