Signs of Glucagon Resistance After a 2-Week Hypercaloric Diet Intervention.

Autor:	Suppli MP; Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, DK-2900 Hellerup, Denmark., Høgedal A; Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, DK-2900 Hellerup, Denmark., Bagger JI; Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, DK-2900 Hellerup, Denmark.; Steno Diabetes Center Copenhagen, DK-2730 Herlev, Denmark., Chabanova E; Department of Radiology, Herlev Hospital, University of Copenhagen, DK-2730 Herlev, Denmark., van Hall G; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.; Clinical Metabolomics Core Facility, Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, Denmark., Forman JL; Section of Biostatistics, Department of Public Health, University of Copenhagen, DK-1353 Copenhagen, Denmark., Christensen MB; Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, DK-2900 Hellerup, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.; Department of Clinical Pharmacology, Bispebjerg Hospital, University of Copenhagen, DK-2400 Copenhagen, Denmark.; Copenhagen Center for Translational Research, Bispebjerg Hospital, University of Copenhagen, DK-2400 Copenhagen, Denmark., Albrechtsen NJW; Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.; Department of Clinical Biochemistry, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, DK-2400 Copenhagen, Denmark., Holst JJ; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark., Knop FK; Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, DK-2900 Hellerup, Denmark.; Steno Diabetes Center Copenhagen, DK-2730 Herlev, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.
Jazyk:	angličtina
Zdroj:	The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2024 Mar 15; Vol. 109 (4), pp. 955-967.
DOI:	10.1210/clinem/dgad666
Abstrakt:	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. (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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