Ghrelin Infusion in Humans Induces Acute Insulin Resistance and Lipolysis Independent of Growth Hormone Signaling

• Published in: Diabetes (New York, N.Y.) Vol. 57; no. 12; pp. 3205 - 3210
• Main Authors: VESTERGAARD, Esben Thyssen, GORMSEN, Lars Christian, JESSEN, Niels, LUND, Sten, HANSEN, Troels Krarup, MOLLER, Niels, JORGENSEN, Jens Otto Lunde
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01-12-2008
• Subjects: Adrenocorticotropic Hormone - drug effects; Adrenocorticotropic Hormone - secretion; Biological and medical sciences; Biopsy; Body fat; Cross-Over Studies; Diabetes; Diabetes. Impaired glucose tolerance; Double-Blind Method; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Ghrelin; Ghrelin - administration & dosage; Ghrelin - blood; Ghrelin - pharmacology; Glucose; Growth Hormone - physiology; Growth hormones; Human subjects; Humans; Hydrocortisone - secretion; Hypopituitarism - blood; Infusions, Intravenous; Insulin resistance; Insulin Resistance - physiology; Kinases; Ligands; Lipolysis; Lipolysis - drug effects; Male; Medical sciences; Metabolism; Middle Aged; Musculoskeletal system; Plasma; Properties; Reference Values; Research design; Risk factors; Signal Transduction; Young Adult; United States; Finland; Endocrinopathy; Human; Target tissue resistance; Somatotropin; Signal transduction; Adenohypophyseal hormone; Ghrelin; Diabetes mellitus; Metabolic diseases; Insulin resistance; Lipolysis
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db08-0025

Ghrelin Infusion in Humans Induces Acute Insulin Resistance and Lipolysis Independent of Growth Hormone Signaling
Esben Thyssen Vestergaard ,
Lars Christian Gormsen ,
Niels Jessen ,
Sten Lund ,
Troels Krarup Hansen ,
Niels Moller and
Jens Otto Lunde Jorgensen
From Medical Department M (Endocrinology and Diabetes), Aarhus University Hospital, Aarhus, Denmark
Corresponding author: Esben Thyssen Vestergaard, etv{at}dadlnet.dk
Abstract
OBJECTIVE— Ghrelin is a gut-derived peptide and an endogenous ligand for the growth hormone (GH) secretagogue receptor. Exogenous ghrelin
stimulates the release of GH (potently) and adrenocorticotropic hormone (ACTH) (moderately). Ghrelin is also orexigenic, but
its impact on substrate metabolism is controversial. We aimed to study direct effects of ghrelin on substrate metabolism and
insulin sensitivity in human subjects.
RESEARCH DESIGN AND METHODS— Six healthy men underwent ghrelin (5 pmol · kg −1 · min −1 ) and saline infusions in a double-blind, cross-over study to study GH signaling proteins in muscle. To circumvent effects
of endogenous GH and ACTH, we performed a similar study in eight hypopituitary adults but replaced with GH and hydrocortisone.
The methods included a hyperinsulinemic-euglycemic clamp, muscle biopsies, microdialysis, and indirect calorimetry.
RESULTS— In healthy subjects, ghrelin-induced GH secretion translated into acute GH receptor signaling in muscle. In the absence of
GH and cortisol secretion, ghrelin acutely decreased peripheral, but not hepatic, insulin sensitivity together with stimulation
of lipolysis. These effects occurred without detectable suppression of AMP-activated protein kinase phosphorylation (an alleged
second messenger for ghrelin) in skeletal muscle.
CONCLUSIONS— Ghrelin infusion acutely induces lipolysis and insulin resistance independently of GH and cortisol. We hypothesize that the
metabolic effects of ghrelin provide a means to partition glucose to glucose-dependent tissues during conditions of energy
shortage.
Footnotes
Published ahead of print at http://diabetes.diabetesjournals.org on 5 September 2008. Clinical trial reg. nos. NCT00116025 and NCT00139945, clinicaltrials.gov.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work
is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Accepted August 26, 2008.
Received January 8, 2008.
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