As for many other hormones, insulin binding to specific receptors on plasma membrane of target cells represents the first step in hormone action. Knowledge of the mechanisms controlling hormone-receptor complexes, as well as of the pathophysiology of insulin receptors is of relevant importance for a correct understanding of many metabolic disorders. Insulin receptors are glycoproteins, have a molecular weight of approximately 300,000 and are located in the plasma membrane. Insulin binding to receptors is specific, rapid, reversible and saturable. The main characteristics of insulin receptors in a given tissue are the binding capacity, depending on the number of receptors present, and the binding affinity. On target cells two separate classes of insulin receptors have been postulated: one with high capacity and low affinity, and the other one with low capacity and high affinity. Alternatively, it is possible that only one receptor type exists, with a binding affinity which varies inversely to the number of occupied receptors. The affinity is mainly regulated by the physical and chemical properties of the environment, while the receptor number is inversely controlled by the circulating levels of insulin, this latter phenomenon being called 'down regulation'. There is evidence that after the formation of the hormone-receptor complex the insulin molecule is internalized within the cell. It is not known whether such internalization is related to the presence of other, distinct, specific receptors for insulin that have been demonstrated in various intracellular organelles (nucleus, endoplasmatic reticulum, Golgi apparatus). The significance of these intracellular insulin receptors is presently unclear. From a clinical point of view, the reduction in insulin receptors, which occurs in all hyperinsulinemic states due to the 'down regulation', plays an important role in the vicious circle responsible for the maintainance or the worsening of insulin resistance until the development of overt metabolic derangements. Also of interest is the characterization of a syndrome with extraordinary insulin resistance associated with acanthosis nigricans, entirely due to the presence of a circulating autoantibody against insulin receptors. Finally, it has been proposed that the therapeutic action of a class of hypoglycemic agents, the biguanides, may be at least partially explained by an increased binding of insulin to its receptors induced by these drugs.
|Translated title of the contribution||The insulin receptors|
|Number of pages||15|
|Journal||Giornale Italiano di Diabetologia|
|Publication status||Published - 1982|
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Internal Medicine