title: Ghrelin infusion in humans induces acute insulin resistance and lipolysis independent of growth hormone signaling.
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.
  
  
  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.
authors.affiliation: Medical Department M (Endocrinology and Diabetes), Aarhus University Hospital, Aarhus, Denmark. etv@dadlnet.dk
authors.forename: Esben Thyssen
authors.initials: ET
authors.lastname: Vestergaard
authors.forename: Lars Christian
authors.initials: LC
authors.lastname: Gormsen
authors.forename: Niels
authors.initials: N
authors.lastname: Jessen
authors.forename: Sten
authors.initials: S
authors.lastname: Lund
authors.forename: Troels Krarup
authors.initials: TK
authors.lastname: Hansen
authors.forename: Niels
authors.initials: N
authors.lastname: Moller
authors.forename: Jens Otto Lunde
authors.initials: JO
authors.lastname: Jorgensen
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000187:drug effects / Q000378:metabolism; D018592:Cross-Over Studies; D004311:Double-Blind Method; D054439:Ghrelin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D013006:Growth Hormone / Q000502:physiology*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007018:Hypopituitarism / Q000097:blood*; D007262:Infusions, Intravenous; D007333:Insulin Resistance / Q000502:physiology*; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D015398:Signal Transduction; D055815:Young Adult
chemical_list: D054439:Ghrelin; D000324:Adrenocorticotropic Hormone; D013006:Growth Hormone; D006854:Hydrocortisone
references.citation: J Clin Endocrinol Metab. 2006 Jul;91(7):2574-81
references.pmid: 16621911
references.citation: Diabetes. 1981 Dec;30(12):1000-7
references.pmid: 7030826
references.citation: J Clin Endocrinol Metab. 2000 Oct;85(10):3803-7
references.pmid: 11061542
references.citation: Am J Physiol. 1999 Nov;277(5):E848-54
references.pmid: 10567011
references.citation: Metabolism. 1988 Mar;37(3):287-301
references.pmid: 3278194
references.citation: Am J Physiol Endocrinol Metab. 2005 Jan;288(1):E228-35
references.pmid: 15328073
references.citation: Regul Pept. 2005 Mar 15;126(1-2):67-71
references.pmid: 15620416
references.citation: Annu Rev Biochem. 1998;67:821-55
references.pmid: 9759505
references.citation: J Chromatogr. 1982 Mar 12;228:143-54
references.pmid: 7076741
references.citation: Cell Metab. 2006 May;3(5):379-86
references.pmid: 16679295
references.citation: J Clin Endocrinol Metab. 2000 Dec;85(12):4908-11
references.pmid: 11134161
references.citation: J Clin Endocrinol Metab. 2005 Feb;90(2):741-6
references.pmid: 15522942
references.citation: Am J Physiol Endocrinol Metab. 2007 Jun;292(6):E1829-36
references.pmid: 17311892
references.citation: J Biol Chem. 2004 Mar 26;279(13):12005-8
references.pmid: 14742438
references.citation: J Clin Endocrinol Metab. 2001 Dec;86(12):5992
references.pmid: 11739476
references.citation: Am J Physiol Gastrointest Liver Physiol. 2008 Mar;294(3):G610-8
references.pmid: 18048479
references.citation: Regul Pept. 2004 Aug 15;120(1-3):23-32
references.pmid: 15177917
references.citation: J Clin Endocrinol Metab. 2004 Oct;89(10):5035-42
references.pmid: 15472202
references.citation: Diabetes. 2006 Dec;55(12):3486-93
references.pmid: 17130496
references.citation: J Clin Endocrinol Metab. 2008 Feb;93(2):438-44
references.pmid: 18042651
references.citation: J Appl Physiol (1985). 1996 Oct;81(4):1501-9
references.pmid: 8904560
references.citation: J Biol Chem. 2005 Jul 1;280(26):25196-201
references.pmid: 15899896
references.citation: Ann N Y Acad Sci. 1959 Sep 25;82:420-30
references.pmid: 13833973
references.citation: Diabetologia. 1983 May;24(5):359-65
references.pmid: 6307793
references.citation: Nutr Metab Cardiovasc Dis. 2005 Dec;15(6):410-7
references.pmid: 16314227