RECEPTOR-COUPLED INFORMATION PROCESSES IN THE REGULATION OF PANCREATIC BETA-CELL FUNCTIONS BY THE ALIMENTARY-TRACT

Thirty years ago, the regulatory role of beta-cell functions by the al imentary tract were summarized into the concept of ''enteroinsular-axi s'' (85, 405). Since then the complexity of the system has increased c onsiderably (5, 85, 173, 340, 433) and involves many recently discover ed substances (37, 60, 78, 120, 272, 322, 341, 395, 421, 448, 452). Th e regulation of the beta-cell function includes signals released into the blood stream during the ingestion of food, as nutrients absorbed a nd gastrointestinal hormones and neuro-transmitters present in pancrea tic nerve endings. It includes also a controversial but possible parac rine regulation by messengers releases from non beta-cells (50, 133, 2 62, 381) and an autocrine regulation by substances released from beta- cells (42, 45, 222, 237, 266, 378). The delivery of these informations to beta(-)cell is sequentially coordinated according to the fasting/f eeding rhythm and involves neutrotransmitters released during the ceph alic phase and gastrointestinal hormones released during the food inge stion from the gastroduodenum to the intestine. However, the rythm in the release of the alimentary tract signals cannot fully explain the o verall regulation of the pancreatic beta-cell function due to the dige stion of food. Different kinds of physiological stress as exercise (10 8, 400), development (62, 219, 310) and overweight (444) are also dire ctly involved in the regulation of insulin synthesis and secretion thr ough both nerve activation and the release of different hormones. Furt her, beta-cell mass vary according to the insulin need of the body (15 9). Growth promoting peptides together with substrates intervene throu gh still unknown transduction systems to modulate the size of cellular proliferative compartments leading to functional beta-cells (51, 59, 159). Therefore, a particular regulation by the alimentary tract canno t today be isolated from the other regulatory pathways. The fine adjus tment of plasma insulin levels involves a coordination which mainly op erate at the level of the beta-cell receptors, through specific bindin g of distinct signals to the beta-cell plasma membrane and sequential transduction to specific cellular responses. In the further paragraphs we will see the transduction systems underlying the remarkably divers e signaling system of the beta-cells. We will try to determine the mec hanisms by which the information processed from specific binding sites to an adequate cellular response. Further, we will also discuss the i nteraction points both between the different transduction systems of t he beta-cell and between these transduction systems and glucose, the p rimary regulator of beta-cell function. Last but not least, we will se e how the study of these systems which deepened our knowledges of the normal function of the beta-cell might hopefully lead to a better unde rstanding of the pathology of diabetes.