Glucose Memory of Pancreatic B and A2 Cells: EVIDENCE FOR COMMON TIME-DEPENDENT ACTIONS OF GLUCOSE ON INSULIN AND GLUCAGON SECRETION IN THE PERFUSED RAT PANCREAS

The influence of previous exposure to glucose on the subsequent B- and A(2)-cell secretory responses to arginine was investigated in the perfused pancreas of the rat. Arginine (8 mM) was administered in two brief (9 min) pulses separated by a period of 66 min. In pancreata from 18-h-fasted animals the two pulses of arginine elicited biphasic glucagon secretory responses, while stimulation of insulin release was barely detectable. When 27.7 mM glucose was administered for 30 min during the intervening period up to 20 min before the second pulse of arginine, the glucagon response to arginine was diminished by 55% while the insulin release was markedly increased in comparison with the first pulse. 8.3 mM glucose, when administered before the second pulse of arginine, exerted effects that were smaller but otherwise similar to those of 27.7 mM glucose.The inclusion of 3.9 mM glucose during the stimulation periods with arginine decreased the glucagon and greatly increased the insulin secretory response. Under these conditions, previous exposure to 27.7 mM glucose inhibited the glucagon and enhanced the insulin response to the second stimulatory pulse of arginine to the same relative degree as when arginine was administered alone.Diazoxide (2 mM), when administered together with 27.7 mM glucose, almost completely inhibited insulin release induced by the presence of glucose, yet did not influence the modulation exerted by glucose on the subsequent insulin and glucagon secretory response to arginine. Conversely, these effects of the glucose pulse could not be reproduced by 1 mug/ml of porcine insulin. Previous exposure to glyceraldehyde (10 mM) mimicked the glucose effects.Also, in pancreata from fed rats, previous exposure to 27.7 mM glucose markedly inhibited subsequent arginine-induced glucagon secretion while the concomittant insulin response was enhanced.IT IS CONCLUDED THAT: (a) both A(2)- and B-cell responsiveness is modulated by a previous exposure to glucose which produces opposite effects in the two cell types, (b) this action of glucose does not depend on its insulin-releasing capacity, and (c) instead, a "memory" of glucose is induced as a consequence of the metabolism of the sugar in the A(2) and B cells.