Physiology &Behavior, Vol. 52, pp. 1193-1196, 1992 0031-9384/92$5.00 + .00 Printedin the USA. Copyright© 1992PergamonPressLtd. MINIREVIEW Long-Term Regulation of Pancreatic B-Cell Responsiveness to D-Glucose by Food Availability, Feeding Schedule, and Diet Composition A. R. CARPINELLI, R. CURI AND W. J. MALAISSE l Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, 05508 Sao Paulo (SP), Brazil and Laboratory of Experimental Medicine, Erasmus Medical School, Brussels Free University, B-1070 Brussels, Belgium Received 23 March 1992 CARPINELLI, A. R., R. CURl AND W. J. MALAISSE. Long-term regulation ofpancreatic B-cellresponsivenessto D-glucose by food availability, feedingschedule,anddietcomposition. PHYSIOLBEHAV52(6) 1193-1196, 1992.--The immediate metabolic, cationic, and secretory response of the insulin-producing B-cellto D-glucoseis regulated, in a delayed or long-term manner, by nutritional factors such as food availability, feedingschedule, or diet composition.The B-cellkeeps the memory of these nutritional manipulations so that the corresponding changes in its responsivenessto D-glucose can be documented in vitro in isolated pancreatic islets. The results of experiments conducted in starved rats, in animals exposed to an altered feeding schedule, and in rats given free access to a high-carbohydrate,high-protein, or high-lipid,as distinct from balanced, diet all suggestthat a sufficient prandial hyperglycemiais essentialfor maintenance of an optimal metabolic and secretory behavior of the islet B-cell in response to a rise in D-glucoseconcentration. Insulin secretion Islet cells Starvation Feeding schedule Diet composition GLUCOSE homeostasis requires a continuous and continuously adjusted supply of pancreatic insulin (16). In this respect, a rapid and sufficiently marked increase in insulin output in response to hyperglycemia appears as an essential feature of the pancreatic B-cell normal secretory behavior. The capacity of D-glucose to stimulate insulin release is causally linked to the catabolism of the hexose in the islet B-cells through changes in K + permeability and Ca2+ influx (21). The metabolic, cationic, and secretory re- sponse of the B-cell to a sudden increase in D-glucose extracellular concentration is modulated, in a delayed or long-term manner, by a number of ontogenic, nutritional, and endocrine factors (15). In the light of prior experiments dealing with the effects of starvation, alteration in feeding schedule, and changes in diet composition upon several variables of islet function, it is pro- posed in the present minireview that the long-term nutritional regulation of the B-cell secretory responsiveness to D-glucose is critically dependent on the occurrence of an appropriate prandial hyperglycemia. EFFECT OF STARVATION It has long been known that islets prepared from starved an- imals display a decreased insulin biosynthetic (7) and secretory (4,20) response to D-glucose. The insulinotropic action of other nutrient or nonnutrient secretagogues is, as a rule, less markedly affected (11,13,27,30). Within limits, therefore, starvation may be considered as an experimental model in which there is a preferential impairment of the B-cell responsiveness to D-glucose, a situation analogous to that thought to prevail in noninsulin- dependent diabetes and even in the preclinical stage of insulin- dependent diabetes (6,12). It was then shown that the utilization of D-glucose is also impaired in islets from starved rats, whereas the metabolism of D-glyceraldehyde is little affected by starvation (13,31,32). These findings led to the proposal that starvation might decrease the activity or altered the kinetic properties of key enzymes, such as glucokinase and phosphofructokinase, in the early steps of glycolysis (10). The activity of glucokinase and phosphofructo- kinase was later found to be, indeed, decreased in islet homog- enates from starved rats (1,2,22). Further work then led to the view that, in the B-cell, glucokinase represents a glucose-inducible enzyme rather than being insulin inducible, as in hepatocytes. For instance, the intravenous administration of D-glUCOSeloads and resulting bursts of hyperglycemia were found to prevent the starvation-induced decrease in B-cell secretory activity, even Requests for reprints should be addressed to Willy J. Malaisse, Laboratory of Experimental Medicine, Brussels Free University, 808 Route de Lennik, B-1070 Brussels,Belgium. 1193