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Ghrelin suppresses glucose-stimulated insulin secretion and deteriorates glucose tolerance in healthy humans.

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Date
2010-09
Authors
Tong, Jenny
Prigeon, Ronald L
Davis, Harold W
Bidlingmaier, Martin
Kahn, Steven E
Cummings, David E
Tschöp, Matthias H
D'Alessio, David
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Abstract
OBJECTIVE: The orexigenic gut hormone ghrelin and its receptor are present in pancreatic islets. Although ghrelin reduces insulin secretion in rodents, its effect on insulin secretion in humans has not been established. The goal of this study was to test the hypothesis that circulating ghrelin suppresses glucose-stimulated insulin secretion in healthy subjects. RESEARCH DESIGN AND METHODS: Ghrelin (0.3, 0.9 and 1.5 nmol/kg/h) or saline was infused for more than 65 min in 12 healthy patients (8 male/4 female) on 4 separate occasions in a counterbalanced fashion. An intravenous glucose tolerance test was performed during steady state plasma ghrelin levels. The acute insulin response to intravenous glucose (AIRg) was calculated from plasma insulin concentrations between 2 and 10 min after the glucose bolus. Intravenous glucose tolerance was measured as the glucose disappearance constant (Kg) from 10 to 30 min. RESULTS: The three ghrelin infusions raised plasma total ghrelin concentrations to 4-, 15-, and 23-fold above the fasting level, respectively. Ghrelin infusion did not alter fasting plasma insulin or glucose, but compared with saline, the 0.3, 0.9, and 1.5 nmol/kg/h doses decreased AIRg (2,152 +/- 448 vs. 1,478 +/- 2,889, 1,419 +/- 275, and 1,120 +/- 174 pmol/l) and Kg (0.3 and 1.5 nmol/kg/h doses only) significantly (P < 0.05 for all). Ghrelin infusion raised plasma growth hormone and serum cortisol concentrations significantly (P < 0.001 for both), but had no effect on glucagon, epinephrine, or norepinephrine levels (P = 0.44, 0.74, and 0.48, respectively). CONCLUSIONS: This is a robust proof-of-concept study showing that exogenous ghrelin reduces glucose-stimulated insulin secretion and glucose disappearance in healthy humans. Our findings raise the possibility that endogenous ghrelin has a role in physiologic insulin secretion, and that ghrelin antagonists could improve beta-cell function.
Type
Journal article
Subject
Adolescent
Adult
Blood Glucose
Female
Ghrelin
Glucose
Glucose Tolerance Test
Growth Hormone
Humans
Hydrocortisone
Insulin
Male
Middle Aged
Reference Values
Young Adult
Permalink
https://hdl.handle.net/10161/12641
Published Version (Please cite this version)
10.2337/db10-0504
Publication Info
Tong, Jenny; Prigeon, Ronald L; Davis, Harold W; Bidlingmaier, Martin; Kahn, Steven E; Cummings, David E; ... D'Alessio, David (2010). Ghrelin suppresses glucose-stimulated insulin secretion and deteriorates glucose tolerance in healthy humans. Diabetes, 59(9). pp. 2145-2151. 10.2337/db10-0504. Retrieved from https://hdl.handle.net/10161/12641.
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Scholars@Duke

D'Alessio

David A D'Alessio

Professor of Medicine
Tong

Jenny Tong

Associate Professor of Medicine
This author no longer has a Scholars@Duke profile, so the information shown here reflects their Duke status at the time this item was deposited.
Alphabetical list of authors with Scholars@Duke profiles.
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