[Insulin resistance. Physiopathological and biochemical aspects]

New dimensions have been acquired in the physiopathology of insulin-resistant syndromes, by measurement of insulin receptors and advances in knowledge of their structure and function. The insulin-resistance of obese subjects and non-insulin dependent diabetics is related to both a reduction in the number of receptors, responsible for diminished sensitivity to insulin, and alterations in the action of the hormone at the post-receptor stage, with resulting suppression of the maximal response to insulin. The number of receptors varies as a function of blood insulin levels, hyperinsulinism being associated with a reduction in their number (negative feed-back). Post-receptor stages appear to be particularly sensitive to either absolute (insulin-dependent diabetes) or relative (non-insulin dependent diabetes) insulinopenia. The rare syndromes of extreme insulin resistance, often accompanied by acanthosis nigricans, represent a heterogeneous collection divisible into 3 sub-groups. In type A there is reduced insulin binding related to a possible primary anomaly (genetic) of the receptor. Type B is characterized by the presence of serum auto-antibodies directed against the receptor, while in type C the anomalies exist at the post-receptor stage. Insulin accelerates degradation of its specific receptor, a mechanism capable of explaining (at least partly) the negative feed-back control of the receptor by the hormone. The insulin-receptor complexes undergo intracellular transfer and a return to the plasmic membrane, but possible physiopathological implications of this movement have not been established. The receptor includes two principal glycoprotein subunits; alpha (130 kilodaltons) and beta (95 kilodaltons).(ABSTRACT TRUNCATED AT 250 WORDS)