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

dc.contributor.author

Tong, Jenny

dc.contributor.author

Prigeon, Ronald L

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Davis, Harold W

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Bidlingmaier, Martin

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Kahn, Steven E

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Cummings, David E

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Tschöp, Matthias H

dc.contributor.author

D'Alessio, David

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United States

dc.date.accessioned

2016-08-10T20:49:01Z

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2010-09

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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.

dc.identifier

http://www.ncbi.nlm.nih.gov/pubmed/20584998

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db10-0504

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1939-327X

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https://hdl.handle.net/10161/12641

dc.language

eng

dc.publisher

American Diabetes Association

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Diabetes

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10.2337/db10-0504

dc.subject

Adolescent

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Adult

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Blood Glucose

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Female

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Ghrelin

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Glucose

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Glucose Tolerance Test

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Growth Hormone

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Humans

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Hydrocortisone

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Insulin

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Male

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Middle Aged

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Reference Values

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Young Adult

dc.title

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

dc.type

Journal article

duke.contributor.orcid

D'Alessio, David|0000-0003-4155-4870

pubs.author-url

http://www.ncbi.nlm.nih.gov/pubmed/20584998

pubs.begin-page

2145

pubs.end-page

2151

pubs.issue

9

pubs.organisational-group

Clinical Science Departments

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Duke

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Duke Molecular Physiology Institute

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Institutes and Centers

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Medicine

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Medicine, Endocrinology, Metabolism, and Nutrition

pubs.organisational-group

School of Medicine

pubs.publication-status

Published

pubs.volume

59

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