title: Failure of islet amyloid polypeptide to inhibit basal and glucose-stimulated insulin secretion in model experiments in mice and rats.
abstract: Islet amyloid polypeptide (IAPP), also known as amylin, has previously been demonstrated to occur in amyloid deposits in pancreatic islets in type 2 diabetics, and, therefore, the peptide has been suggested to be involved in the pathogenesis of diabetes. The 37 amino acid peptide shows approximately 50% homology with the intrapancreatic neuropeptide calcitonin gene-related peptide (CGRP), a peptide that inhibits insulin secretion. We therefore examined, in model experiments in mice and rats, if IAPP also exerts this effect. IAPP was given intravenously, at dose levels at which CGRP previously has been shown to inhibit insulin secretion. Thus, in mice, IAPP was injected at 0.85 and 4.25 nmol kg-1, and in rats IAPP was infused at 17 or 68 pmol min-1. However, neither basal nor glucose-stimulated insulin release was inhibited by IAPP under these experimental conditions. We also investigated if IAPP (10(-11) to 10(-6) M), when incubated in vitro with isolated, overnight-cultured rat islets, could affect insulin secretion induced by glucose (3.3, 8.3 or 11.7 mM). However, also in vitro no effect by IAPP on insulin release was observed. Hence, in mice and rats, IAPP does not inhibit insulin secretion under experimental conditions identical to those previously used to demonstrate an inhibition by CGRP. Therefore, we conclude (1) that the homologous amino acid sequence within IAPP and CGRP does not seem to be sufficient for inducing inhibition of insulin release in mice and rats and (2) that the possible involvement of IAPP in the pathogenesis of diabetes type 2 still remains speculative.
authors.affiliation: Department of Pharmacology, University of Lund, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Pettersson
authors.forename: B
authors.initials: B
authors.lastname: Ahrén
mesh_terms: D000682:Amyloid / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology; D005260:Female; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000682:Amyloid; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D005947:Glucose