Amylin inhibits glucose-induced insulin secretion in a dose-dependent manner. Study in the perfused rat pancreas

Islet amyloid polypeptide (IAPP), also called amylin, has been localized in the B-cell secretory granule and is co-secreted with insulin. We have investigated the effect of synthetic amidated rat amylin on the insulin release evoked by 9 mM glucose in the isolated, perfused rat pancreas. Amylin, in a range of 75 nM-75 pM, significantly inhibited this insulin response in a dose-dependent manner. The correlation between the logarithm of amylin concentrations and the percentages of inhibition was highly significant (r = 0.98, P < 0.01). The lowest effective amylin concentration tested (75 pM) is within the range of amylin levels reported for the effluent of the perfused rat pancreas. Finally, pre-infusion of the rat pancreas with a high amylin concentration (75 nM) did not alter the insulin response to glucose, thus excluding a toxic effect of amylin on the B-cell. These observations support the concept that amylin plays a role in the control of insulin secretion.