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. 2024 Jun 5;190(6):446-457.
doi: 10.1093/ejendo/lvae054.

Increased hepatic glucagon sensitivity in totally pancreatectomised patients

Iben Rix  1   2 , Asger B Lund  1   3   4 , Lars F Garvey  1 , Carsten P Hansen  5 , Elizaveta Chabanova  6 , Bolette Hartmann  7   8 , Jens J Holst  7   8 , Tina Vilsbøll  1   3   4 , Gerrit Van Hall  7   9 , Filip K Knop  1   3   4
Affiliations

Increased hepatic glucagon sensitivity in totally pancreatectomised patients

Iben Rix et al. Eur J Endocrinol. .

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.

Keywords: glucagon; metabolism; totally pancreatectomy; type 1 diabetes.

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Conflict of interest statement

Conflict of interest: Co-author A.B.L. has received lecture fees and/or travel/conference from Novo Nordisk, Astra Zeneca and Sanofi. Co-author T.V. has served on scientific advisory panels and/or been part of speaker's bureaus for, served as a consultant to, and/or received research or travel/conference support from Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Gilead, Merck Sharp & Dohme, Mundipharma, Novo Nordisk, Sanofi, and SunPharma. Co-author F.K.K. is employed by Novo Nordisk as of December 1st, 2023. Before joining Novo Nordisk, F.K.K. has served on scientific advisory panels and/or been part of speaker's bureaus for, served as a consultant to, and/or received research or travel/conference support from 89bio, Amgen, AstraZeneca, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, Gubra, MedImmune, MSD/Merck, Mundipharma, Norgine, Novo Nordisk, Sanofi, Zealand Pharma and Zucara. All other authors declare no conflict of interest associated with this manuscript. Co-author F.K.K. is on the editorial board of EJE. He was not involved in the review or editorial process for this paper, on which he is listed as author.

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