Increased hepatic glucagon sensitivity in totally pancreatectomised patients
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Increased hepatic glucagon sensitivity in totally pancreatectomised patients. / Rix, Iben; Lund, Asger B.; Garvey, Lars F.; Hansen, Carsten P.; Chabanova, Elizaveta; Hartmann, Bolette; Holst, Jens J.; Vilsbøll, Tina; Van Hall, Gerrit; Knop, Filip K.
In: European Journal of Endocrinology, Vol. 190, No. 6, 2024, p. 446-457.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Increased hepatic glucagon sensitivity in totally pancreatectomised patients
AU - Rix, Iben
AU - Lund, Asger B.
AU - Garvey, Lars F.
AU - Hansen, Carsten P.
AU - Chabanova, Elizaveta
AU - Hartmann, Bolette
AU - Holst, Jens J.
AU - Vilsbøll, Tina
AU - Van Hall, Gerrit
AU - Knop, Filip K.
N1 - Publisher Copyright: © 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 reprints@oup.com 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
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - glucagon
KW - metabolism
KW - totally pancreatectomy
KW - type 1 diabetes
U2 - 10.1093/ejendo/lvae054
DO - 10.1093/ejendo/lvae054
M3 - Journal article
C2 - 38781444
AN - SCOPUS:85195709606
VL - 190
SP - 446
EP - 457
JO - European Journal of Endocrinology
JF - European Journal of Endocrinology
SN - 0804-4643
IS - 6
ER -
ID: 394989720