[Current data on insulin secretion and its regulation].

Abstract

Glucose is the main stimulator and physiological regulator of insulin secretion. The great sensitivity of the B cell to glucose variations between 1 g/l (5.5 mM) and 3 g/l (16.6 mM) and its rapid response ensure the constant adaptation of its secretion to plasma glucose level. The cellular mechanisms involved in insulin response can be schematically represented in three stages: The first stage is the recognition of the insulinotropic agent. In the case of glucose, this involves its metabolism. The second one is the coupling of the recognition process to activation of the effector system and implies a series of intracellular signals. Coupling factors include metabolites and cofactors, ions, cyclic AMP, polyphosphoinositides. The result of all these cellular events is the increase in cytosolic Ca2+ and the activation of protein-kinases: Ca2+-calmodulin-, cAMP- and Ca2+-phospholipid-dependent protein kinases. The last stage corresponds to a mechanical one, involving granule migration and extrusion. The polymerization of microtubules associated with contraction of microfilaments would cause granule movement. Ca2+-calmodulin-dependent protein kinases would play a major role. While glucose is the main stimulator of insulin secretion, numerous factors can influence it. The regulation of this secretion is essentially under the control of three classes of elements: nutrients, hormones and neurotransmitters. As to stimulation of insulin secretion by nutrients, it seems to be secondary to an increase in intracellular metabolism. However it must be underlined that the insulin secretory effect of most nutrients requires the presence of glucose which is consequently a permissive factor. A number of gastrointestinal and pancreatic hormones stimulate, in presence of glucose, insulin secretion and play an essential role during food intake, which results in a better fitting of insulin secretion to energy supply. The term "incretin" designates a hormonal transmitter between the gastrointestinal tract and the B cell; the "incretin" factors are included in what is termed enteroinsular axis. Of the gastrointestinal hormones, GIP (gastric inhibitory polypeptide) appears to play the most important physiological role in potentiating the insulin secretory effect of glucose. Pancreatic glucagon potentiates the effect of glucose too; it is difficult to distinguish between its endocrine and paracrine role. The pancreatic B cell is under neural regulation. The cholinergic system stimulates insulin secretion and the B cell is fitted with receptors of muscarinic type.(ABSTRACT TRUNCATED AT 400 WORDS)