Influence of glucose concentration on the inhibitory effect of amylin on insulin secretion. Study in the perfused rat pancreas

The effect of amylin on insulin secretion is a matter of controversy. Short-term experiments have shown that amylin, at 75 pmol/l, inhibits the insulin release elicited by a modest increase in the perfusate glucose concentration (from 5.5 mmol/l to 9 mmol/l). The present work was undertaken to further investigate the effect of amylin on glucose-induced insulin release at different glucose concentrations. The study was performed in the isolated perfused rat pancreas. Amylin, at 75 pmol/l, markedly blocked the insulin response when the perfusate glucose concentration was increased from 3.2 mmol/l to 7 mmol/l (by 90%; P<0.01) or from 5.5 mmol/l to 9 mmol/l (by 80%; P<0.01). At the same amylin concentration, no significant inhibition of insulin output was observed when the perfusate glucose level was augmented from 5.5 mmol/l to 16.6 mmol/l, from 7 mmol/l to 11 mmol/l or from 9 mmol/l to 13 mmol/l. At a higher concentration (750 pmol/l), amylin also failed to inhibit the insulin response induced by increasing glucose levels from 5.5 mmol/l to 16.6 mmol/l or from 9 to 13 mmol/l. These findings indicate that, in the rat pancreas, amylin only inhibits insulin release when evoked by elevations of glucose levels comparable to those occurring in normal subjects under physiological conditions. (C) 1997 Elsevier Science B.V.