Esben Thyssen Vestergaard

Ghrelin infusion in humans induces acute insulin resistance and lipolysis independent of growth hormone signaling

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  • Research Laboratory for Biochemical Pathology
  • The Department of Endocrinology and Diabetes
  • Nuklearmedicinsk Afdeling, Aalborg Sygehus
  • Medical Research Laboratory
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.
Original languageEnglish
JournalDiabetes
Volume57
Issue12
Pages (from-to)3205-10
Number of pages5
ISSN0012-1797
DOIs
Publication statusPublished - 2008

    Research areas

  • Adrenocorticotropic Hormone, Cross-Over Studies, Double-Blind Method, Ghrelin, Growth Hormone, Humans, Hydrocortisone, Hypopituitarism, Infusions, Intravenous, Insulin Resistance, Lipolysis, Male, Middle Aged, Reference Values, Signal Transduction, Young Adult

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