Esben Thyssen Vestergaard

Ghrelin does not directly stimulate secretion of glucagon-like peptide-1

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  • Sara Lind Jepsen, Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • ,
  • Esben Thyssen Vestergaard
  • Pierre Larraufie, Metabolic Research Laboratories and Medical Research Council Metabolic Diseases Unit, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, United Kingdom.
  • ,
  • Fiona Mary Gribble, Metabolic Research Laboratories and Medical Research Council Metabolic Diseases Unit, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, United Kingdom.
  • ,
  • Frank Reimann, Metabolic Research Laboratories and Medical Research Council Metabolic Diseases Unit, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, United Kingdom.
  • ,
  • Jens Otto Lunde Jørgensen
  • Jens Juul Holst, Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • ,
  • Rune Ehrenreich Kuhre, Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

CONTEXT: The gastrointestinal hormone ghrelin stimulates growth hormone secretion and appetite, but recent studies indicate that ghrelin also stimulates the secretion of the appetite-inhibiting and insulinotropic hormone glucagon-like peptide-1 (GLP-1). OBJECTIVE: To investigate the putative effect of ghrelin on GLP-1 secretion in vivo and in vitro. SUBJECTS AND METHODS: A randomized placebo-controlled crossover study was performed in eight hypopituitary subjects. Ghrelin or saline was infused intravenously (1 pmol/min × kg) after collection of baseline sample (0 min), and blood was subsequently collected at time 30, 60, 90, and 120 minutes. Mouse small intestine was perfused (n = 6) and GLP-1 output from perfused mouse small intestine was investigated in response to vascular ghrelin administration in the presence and absence of a simultaneous luminal glucose stimulus. Ghrelin receptor expression was quantified in human (n = 11) and mouse L-cells (n = 3) by RNA sequencing and RT-qPCR, respectively. RESULTS: Ghrelin did not affect GLP-1 secretion in humans (area under the curve [AUC; 0-120 min]: ghrelin infusion = 1.37 ± 0.05 min × nmol vs. saline infusion = 1.40 ± 0.06 min × nmol [P = 0.63]), but induced peripheral insulin resistance. Likewise, ghrelin did not stimulate GLP-1 secretion from the perfused mouse small intestine model (mean outputs during baseline/ghrelin infusion = 19.3 ± 1.6/25.5 ± 2.0 fmol/min, n = 6, P = 0.16), whereas glucose-dependent insulinotropic polypeptide administration, used as a positive control, doubled GLP-1 secretion (P < 0.001). Intraluminal glucose increased GLP-1 secretion by 4-fold (P < 0.001), which was not potentiated by ghrelin. Finally, gene expression of the ghrelin receptor was undetectable in mouse L-cells and marginal in human L-cells. CONCLUSIONS: Ghrelin does not interact directly with the L-cell and does not directly affect GLP-1 secretion.

Original languageEnglish
Article numberdgz046
JournalThe Journal of clinical endocrinology and metabolism
Volume105
Issue1
Pages (from-to)266-275
Number of pages10
ISSN0021-972X
DOIs
Publication statusPublished - 1 Jan 2020

Bibliographical note

© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

    Research areas

  • CELLS, GLP-1 SECRETION, GLUCOSE-ABSORPTION, HORMONES, INSULIN-SECRETION, MEAL, MECHANISMS, RECEPTOR, SURGERY, WEIGHT

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