Signs of Glucagon Resistance After a Two-Week Hypercaloric Diet Intervention

Malte Palm Suppli, Astrid Høgedal, Jonatan Ising Bagger, Elizaveta Chabanova, Gerrit van Hall, Julie Lyng Forman, Mikkel Bring Christensen, Nicolai Jacob Wewer Albrechtsen, Jens Juul Holst, Filip Krag Knop*

*Corresponding author af dette arbejde

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2 Citationer (Scopus)

Abstract

Context: Hyperglucagonemia is observed in individuals with obesity and contributes to the hyperglycemia of patients with type 2 diabetes.
Hyperglucagonemia may develop due to steatosis-induced hepatic glucagon resistance resulting in impaired hepatic amino acid turnover and ensuing elevations of circulating glucagonotropic amino acids.
Objective: We evaluated whether glucagon resistance could be induced in healthy individuals by a hypercaloric diet intervention designed to increase hepatic fat content.
Methods: We recruited 20 healthy male individuals to follow a hypercaloric diet and a sedentary lifestyle for 2 weeks. Amino acid concentrations in response to infusion of glucagon were assessed during a pancreatic clamp with somatostatin and basal insulin. The reversibility of any metabolic changes was assessed 8 weeks after the intervention. Hepatic steatosis was assessed by magnetic resonance spectroscopy.
Results: The intervention led to increased hepatic fat content (382% [206%; 705%], P < .01). Glucagon infusion led to a decrease in the concentration of total amino acids on all experimental days, but the percentage change in total amino acids was reduced (−2.5% ± 0.5% vs −0.2% ± 0.7%, P = .015) and the average slope of the decline in the total amino acid concentration was less steep (−2.0 ± 1.2 vs −1.2 ± 0.3 μM/min, P = .016) after the intervention compared to baseline. The changes were normalized at follow-up.
Conclusion: Our results indicate that short-term unhealthy behavior, which increases hepatic fat content, causes a reversible resistance to the effect of glucagon on amino acid concentrations in healthy individuals, which may explain the hyperglucagonemia associated with obesity and diabetes.
OriginalsprogEngelsk
TidsskriftJournal of Clinical Endocrinology and Metabolism
Vol/bind109
Udgave nummer4
Sider (fra-til)955–967
Antal sider13
ISSN0021-972X
DOI
StatusUdgivet - 2024

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© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: [email protected].

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