title: Islet amyloid polypeptide regulates multiple steps in stimulus-secretion coupling of beta cells in rat pancreatic islets.
abstract: Islet amyloid polypeptide (IAPP) is produced in pancreatic beta cells. Intraislet function of IAPP is still uncertain. In the present study, we investigated effects of IAPP and somatostatin on stimulus-secretion coupling of beta cells in isolated rat pancreatic islets. Insulin secretion induced by 22.2 mM glucose was increased by an IAPP antiserum (0.1%) or an IAPP antagonist (IAPP8-37, 10 microM). Pretreatment of islets with pertussis toxin (PTX) abolished the stimulating effect of IAPP8-37 on glucose-induced insulin secretion. In contrast, IAPP antiserum and IAPP8-37 did not change insulin secretion induced by 30 mM KCl. Somatostatin (1 nM) inhibited insulin secretion induced by 22.2 mM glucose, 10 mM L-arginine, 25 microM forskolin, and 200 microM carbachol. IAPP (10 microM) enhanced the inhibitory effect of somatostatin on insulin secretion induced by L-arginine or forskolin. PTX pretreatment abolished the effects of somatostatin and IAPP on arginine-induced insulin secretion. In conclusion, IAPP regulates multiple steps in signal transductions of beta cells. The effects of IAPP on beta cells are mediated by PTX-sensitive regulatory G proteins.
authors.affiliation: Department of Surgery, Karolinska Institute at Huddinge University Hospital, Sweden.
authors.forename: F
authors.initials: F
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Permert
authors.forename: C G
authors.initials: CG
authors.lastname: Ostenson
mesh_terms: D000682:Amyloid / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D004347:Drug Interactions; D005947:Glucose / Q000494:pharmacology; D007106:Immune Sera; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D037342:Pertussis Toxin; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013004:Somatostatin / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D000682:Amyloid; D007106:Immune Sera; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D010446:Peptide Fragments; D010566:Virulence Factors, Bordetella; C079438:islet amyloid polypeptide (8-37); D005576:Colforsin; D013004:Somatostatin; D011189:Potassium Chloride; D002217:Carbachol; D001120:Arginine; D037342:Pertussis Toxin; D005947:Glucose