title: Unacylated ghrelin acts as a potent insulin secretagogue in glucose-stimulated conditions.
abstract: Acylated and unacylated ghrelin (AG and UAG) are gut hormones that exert pleiotropic actions, including regulation of insulin secretion and glucose metabolism. In this study, we investigated whether AG and UAG differentially regulate portal and systemic insulin levels after a glucose load. We studied the effects of the administration of AG (30 nmol/kg), UAG (3 and 30 nmol/kg), the ghrelin receptor antagonist [D-Lys(3)]GHRP-6 (1 micromol/kg), or various combinations of these compounds on portal and systemic levels of glucose and insulin after an intravenous glucose tolerance test (IVGTT, d-glucose 1 g/kg) in anesthetized fasted Wistar rats. UAG administration potently and dose-dependently enhanced the rise of insulin concentration induced by IVGTT in the portal and, to a lesser extent, the systemic circulation. This UAG-induced effect was completely blocked by the coadministration of exogenous AG at equimolar concentrations. Similarly to UAG, [D-Lys(3)]GHRP-6, alone or in combination with AG and UAG, strongly enhanced the portal insulin response to IVGTT, whereas exogenous AG alone did not exert any further effect. Our data demonstrate that, in glucose-stimulated conditions, exogenous UAG acts as a potent insulin secretagogue, whereas endogenous AG exerts a maximal tonic inhibition on glucose-induced insulin release.
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands. c.gauna@erasmus.nl
authors.forename: Carlotta
authors.initials: C
authors.lastname: Gauna
authors.forename: Rosalie M
authors.initials: RM
authors.lastname: Kiewiet
authors.forename: Joop A M J L
authors.initials: JA
authors.lastname: Janssen
authors.forename: Bedette
authors.initials: B
authors.lastname: van de Zande
authors.forename: Patric J D
authors.initials: PJ
authors.lastname: Delhanty
authors.forename: Ezio
authors.initials: E
authors.lastname: Ghigo
authors.forename: Leo J
authors.initials: LJ
authors.lastname: Hofland
authors.forename: Axel P N
authors.initials: AP
authors.lastname: Themmen
authors.forename: Aart Jan
authors.initials: AJ
authors.lastname: van der Lely
mesh_terms: D000107:Acetylation; D000818:Animals; D001786:Blood Glucose / Q000032:analysis*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D054439:Ghrelin; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood*; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D009842:Oligopeptides / Q000008:administration & dosage*; D036361:Peptide Hormones / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D054440:Receptors, Ghrelin
chemical_list: D001786:Blood Glucose; D004338:Drug Combinations; D054439:Ghrelin; D007328:Insulin; D009842:Oligopeptides; D036361:Peptide Hormones; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; C041048:growth hormone releasing hexapeptide