Hyperosmolar Duodenal Saline Infusion Lowers Circulating Ghrelin and Stimulates Intestinal Hormone Release in Young Men

Author:

Veedfald Simon12,Wu Tongzhi1,Bound Michelle1,Grivell Jacqueline1,Hartmann Bolette23,Rehfeld Jens F4,Deacon Carolyn F23,Horowitz Michael1,Holst Jens J23,Rayner Christopher K1

Affiliation:

1. Discipline of Medicine and National Health and Medical Research Council Centre of Research Excellence in Nutritional Physiology, Interventions and Outcomes, University of Adelaide, Adelaide, South Australia, Australia

2. Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

3. Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark

4. Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark

Abstract

AbstractContextThe mechanisms regulating the postprandial suppression of ghrelin secretion remain unclear, but recent observations in rats indicate that an increase in duodenal osmolarity is associated with a reduction in ghrelin levels. Several hormones have been implicated in the regulation of ghrelin.ObjectiveWe hypothesized that intraduodenal infusion of a hyperosmolar solution would lower plasma ghrelin concentrations.Design, Setting, Participants, and InterventionsEighteen healthy young men were studied after an overnight fast on two occasions in a randomized double-blinded fashion. A nasoduodenal catheter was positioned and isoosmolar (300 mOsm/L) or hyperosmolar (1500 mOsm/L) saline was infused intraduodenally (4 mL/min, t = 0 to 45 minutes). Venous blood was sampled at t = −45, −30, −15, 0, 15, 30, 45, 60, 75, 90, 120, and 180 minutes.Main Outcome MeasuresPlasma concentrations of ghrelin, glucagonlike peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), cholecystokinin (CCK), glucagon, pancreatic polypeptide (PP), neurotensin (NT), peptide YY (PYY), motilin, and glucose.ResultsGhrelin concentrations were suppressed with hyperosmolar when compared with isoosmolar saline, and remained lower until t = 180 minutes. CCK, NT, GLP-1, PYY, and glucagon all increased during hyperosmolar, but not isoosmolar, saline infusion (P < 0.01 for all), whereas GIP, PP, and motilin levels were not affected by either infusion.ConclusionsPlasma ghrelin concentrations are lowered, whereas CCK, GLP-1, PYY, NT, and glucagon concentrations are augmented, by hyperosmolar duodenal content in healthy individuals. These observations have implications for the evaluation of studies comparing the effects of different types and loads of nutrients and chemicals on gut hormone secretion.

Funder

Augustinus Fonden

Tømmerhandler Johannes Foghs Fond

Kong Christian den Tiendes Fond

Danish Endocrine Society

National Health and Medical Research Council

Faculty of Medical Sciences, University of Copenhagen

NNF Center for Basic Metabolic Research

Publisher

The Endocrine Society

Subject

Biochemistry, medical,Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism

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