Ghrelin suppresses glucose-stimulated insulin secretion and deteriorates glucose tolerance in healthy humans.
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 articleSubject
AdolescentAdult
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/10161/12641Published Version (Please cite this version)
10.2337/db10-0504Publication 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.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
Collections
More Info
Show full item recordScholars@Duke
David A D'Alessio
James B. Wyngaarden Distinguished Professor of Medicine
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.

Articles written by Duke faculty are made available through the campus open access policy. For more information see: Duke Open Access Policy
Rights for Collection: Scholarly Articles
Works are deposited here by their authors, and represent their research and opinions, not that of Duke University. Some materials and descriptions may include offensive content. More info
Related items
Showing items related by title, author, creator, and subject.
-
The upstream enhancer elements of the G6PC promoter are critical for optimal G6PC expression in murine glycogen storage disease type Ia.
Lee, Young Mok; Pan, Chi-Jiunn; Koeberl, Dwight D; Mansfield, Brian C; Chou, Janice Y (Mol Genet Metab, 2013-11)Glycogen storage disease type-Ia (GSD-Ia) patients deficient in glucose-6-phosphatase-α (G6Pase-α or G6PC) manifest impaired glucose homeostasis characterized by fasting hypoglycemia, growth retardation, hepatomegaly, ... -
Extracellular Matrix Remodeling Regulates Glucose Metabolism through TXNIP Destabilization.
Sullivan, William J; Mullen, Peter J; Schmid, Ernst W; Flores, Aimee; Momcilovic, Milica; Sharpley, Mark S; Jelinek, David; ... (18 authors) (Cell, 2018-09-06)The metabolic state of a cell is influenced by cell-extrinsic factors, including nutrient availability and growth factor signaling. Here, we present extracellular matrix (ECM) remodeling as another fundamental node ... -
Implant healing in experimental animal models of diabetes.
Le, NN; Rose, MB; Levinson, H; Klitzman, B (J Diabetes Sci Technol, 2011-05-01)Diabetes mellitus is becoming increasingly prevalent worldwide. Additionally, there is an increasing number of patients receiving implantable devices such as glucose sensors and orthopedic implants. Thus, it is likely that ...