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 β-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 μM 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 ho 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 β-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.