The effect of exogenous glucagon on circulating amino acids in individuals with and without type 2 diabetes and obesity.

Autor:	Grøndahl MFG; Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark., Bagger JI; Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.; Clinical Research, Steno Diabetes Center Copenhagen, Herlev, Denmark., Suppli MP; Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark., Van Hall G; Department of Clinical Biochemistry, Clinical Metabolomics Core Facility, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Albrechtsen NJW; Department of Clinical Biochemistry, University Hospital Copenhagen, Bispebjerg, Copenhagen, Denmark., Holst JJ; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Vilsbøll T; Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.; Clinical Research, Steno Diabetes Center Copenhagen, Herlev, Denmark., Christensen MB; Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Department of Clinical Pharmacology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark.; Copenhagen Center for Translational Research, Copenhagen University Hospital - Bispebjerg and Frederiksberg, University of Copenhagen, Copenhagen, Denmark., Lund AB; Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark., Knop FK; Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.; Clinical Research, Steno Diabetes Center Copenhagen, Herlev, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Jazyk:	angličtina
Zdroj:	Endocrine connections [Endocr Connect] 2024 Feb 21; Vol. 13 (3). Date of Electronic Publication: 2024 Feb 21 (Print Publication: 2024).
DOI:	10.1530/EC-23-0516
Abstrakt:	Objective: In obesity and type 2 diabetes, hyperglucagonaemia may be caused by elevated levels of glucagonotropic amino acids due to hepatic glucagon resistance at the level of amino acid turnover. Here, we investigated the effect of exogenous glucagon on circulating amino acids in obese and non-obese individuals with and without type 2 diabetes. Design: This was a post hoc analysis in a glucagon infusion study performed in individuals with type 2 diabetes (n = 16) and in age, sex, and body mass index-matched control individuals without diabetes (n = 16). Each group comprised two subgroups of eight individuals with and without obesity, respectively. Methods: All participants received a 1-h glucagon infusion (4 ng/kg/min) in the overnight fasted state. Plasma amino acid concentrations were measured with frequent intervals. Results: Compared to the control subgroup without obesity, baseline total amino acid levels were elevated in the control subgroup with obesity and in the type 2 diabetes subgroup without obesity. In all subgroups, amino acid levels decreased by up to 20% in response to glucagon infusion, which resulted in high physiological steady-state glucagon levels (mean concentration: 74 pmol/L, 95% CI [68;79] pmol/L). Following correction for multiple testing, no intergroup differences in changes in amino acid levels reached significance. Conclusion: Obesity and type 2 diabetes status was associated with elevated fasting levels of total amino acids. The glucagon infusion decreased circulating amino acid levels similarly in all subgroups, without significant differences in the response to exogenous glucagon between individuals with and without obesity and type 2 diabetes. Significance Statement: The hormone glucagon stimulates glucose production from the liver, which may promote hyperglycaemia if glucagon levels are abnormally elevated, as is often seen in type 2 diabetes and obesity. Glucagon levels are closely linked to, and influenced by, the levels of circulating amino acids. To further investigate this link, we measured amino acid levels in individuals with and without obesity and type 2 diabetes before and during an infusion of glucagon. We found that circulating amino acid levels were higher in type 2 diabetes and obesity, and that glucagon infusion decreased amino acid levels in both individuals with and without type 2 diabetes and obesity. The study adds novel information to the link between circulating levels of glucagon and amino acids.
Databáze:	MEDLINE
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