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.