Glucose Memory of Pancreatic B and A2 Cells

Abstract

A B S T R A C T The influence of previous exposure to glucose on the subsequent B-and A2-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 ,ug/ml of porcine

Pancreastatin (33–49) enhances the priming effect of glucose in the rat pancreas

“…However, pancreastatin significantly increased (p < 0.05) the enhanced insulin response to a second pulse of 16.7 mM glucose. These results agree with the time-dependent potentiation or memory of the B cell response by glucose as described in literature 1~ 13,14 and suggests a role for pancreastatin in the adaptation of the B cell to glucose stimulation of insulin secretion. As expected 1, pancreastatin did not modify the rate of insulin secretion when the glucose concentration of the perfusion medium was 2.7 mM, showing a lack of effect on non-stimulated insulin release.…”

Priming effect of glucagon-like peptide-1 (7–36) amide, glucose-dependent insulinotropic polypeptide and cholecystokinin-8 at the isolated perfused rat pancreas

“…It is well established that prior exposure to glucose sensitizes the endocrine pancreas to a subsequent glucose stimulus [3][4][5][6][7]. This 'memory' for a previous glucose stimulation was shown to be both time and dosedependently.…”

“…This 'memory' for a previous glucose stimulation was shown to be both time and dosedependently. It was observed in several species, including man [3][4][5][6][7][8][9][10], and there is no evidence that the islet memory described for glucose is due to the release of intestinal peptides and subsequent effects on the beta cell.…”

A la recherche du temps perdu — epilogue to the Minkowski award lecture 1974

“…It is an attractive thought that the calcium-lowering effect of glucose described by Hellman et al could be responsible for the reduced insulin response during time-dependent inhibition; this hypothesis has not yet been tested. We demonstrated that inhibition of glucose metabolism with mannoheptulose blocked time-dependent potentiation, whereas suppressors of insulin release, such as adrenaline, somatostatin or diazoxide had no effect [34,38,39,65]. We concluded therefore that metabolism of glucose was necessary for time-dependent potentiation.…”

“…Although the t 89 of time-dependent inhibition is not known precisely, it is definitely of the order of several minutes and quite different from that of acute stimulus-secretion coupling [33][34][35]. 3The third event, slower in onset, amplifies the insulin response with time, and thus is responsible for the late increase in the secretion rate [36][37][38][39]. We have named this phenomenon time-dependent potentiation; its t 89 is also quite long.…”