INFLUENCE OF ISLET AMYLOID POLYPEPTIDE AND THE 8-37 FRAGMENT OF ISLET AMYLOID POLYPEPTIDE ON INSULIN RELEASE FROM PERIFUSED RAT ISLETS

IAPP, or amylin, is a 37-amino acid peptide that is co-secreted with insulin from the pancreatic beta-cells. We have determined the effects of IAPP and the antagonist 8-37 fragment of IAPP on the secretion of insulin from isolated rat islets studied in a perifusion system. Insulin secretion was stimulated by 8 mM glucose and 0.2 muM carbachol. IAPP at 10(-7) M reduced insulin release by 32% from 7.1 (95% Cl 5.8-8.6) to 4.8 (3.0-7.5) fmol . min-1 . islet-1 (P = 0.046, n = 7). IAPP at 1.5 . 10(-6) M reduced insulin release by 62% from 6.5 (3.4-12.3) to 2.5 (1.4-4.4) fmol . min-1 . islet-1 (P = 0.001, n = 6). IAPP at 10(-5) M decreased insulin release by 70% (P < 0.001, n = 6). When IAPP(8-37) at 10(-5) M was added to IAPP at 1.5 . 10(-6) M, there was only a 22% reduction of insulin release (P = 0.06, n = 6) compared with control chambers with no peptide added. This reduction was less (P = 0.002) than observed with IAPP (1.5 . 10(-6) M) alone. IAPP(8-37) at 4 . 10(-5) M in the absence of exogenously added IAPP increased insulin secretion by 48% (P = 0.01, n = 6), but IAPP(8-37) at 10(-5) M did not alter insulin secretion. These findings demonstrate that IAPP decreases insulin secretion from islet beta-cells, an effect that can be antagonized by the 8-37 fragment of IAPP. The ability of the 8-37 fragment of IAPP alone to increase insulin secretion suggests the possibility that endogenously released IAPP has a tonic inhibitory effect on insulin secretion under the conditions tested.