Increased hepatic glucagon sensitivity in totally pancreatectomised patients

Iben Rix, Asger B. Lund, Lars F. Garvey, Carsten P. Hansen, Elizaveta Chabanova, Bolette Hartmann, Jens J. Holst, Tina Vilsbøll, Gerrit Van Hall, Filip K. Knop*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

OBJECTIVE: The metabolic phenotype of totally pancreatectomised patients includes hyperaminoacidaemia and predisposition to hypoglycaemia and hepatic lipid accumulation. We aimed to investigate whether the loss of pancreatic glucagon may be responsible for these changes. METHODS: Nine middle-aged, normal-weight totally pancreatectomised patients, nine patients with type 1 diabetes (C-peptide negative), and nine matched controls underwent two separate experimental days, each involving a 150-min intravenous infusion of glucagon (4 ng/kg/min) or placebo (saline) under fasting conditions while any basal insulin treatment was continued. RESULTS: Glucagon infusion increased plasma glucagon to similar high physiological levels in all groups. The infusion increased hepatic glucose production and decreased plasma concentration of most amino acids in all groups, with more pronounced effects in the totally pancreatectomised patients compared with the other groups. Glucagon infusion diminished fatty acid re-esterification and tended to decrease plasma concentrations of fatty acids in the totally pancreatectomised patients but not in the type 1 diabetes patients. CONCLUSION: Totally pancreatectomised patients were characterised by increased sensitivity to exogenous glucagon at the level of hepatic glucose, amino acid, and lipid metabolism, suggesting that the metabolic disturbances characterising these patients may be rooted in perturbed hepatic processes normally controlled by pancreatic glucagon.

Original languageEnglish
JournalEuropean Journal of Endocrinology
Volume190
Issue number6
Pages (from-to)446-457
Number of pages12
ISSN0804-4643
DOIs
Publication statusPublished - 2024

Bibliographical note

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© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact

Keywords

  • glucagon
  • metabolism
  • totally pancreatectomy
  • type 1 diabetes

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