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

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 elevation...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:The journal of clinical endocrinology and metabolism 2024-03, Vol.109 (4), p.955-967
Hauptverfasser: Suppli, Malte Palm, Høgedal, Astrid, Bagger, Jonatan Ising, Chabanova, Elizaveta, van Hall, Gerrit, Forman, Julie Lyng, Christensen, Mikkel Bring, Albrechtsen, Nicolai Jacob Wewer, Holst, Jens Juul, Knop, Filip Krag
Format: Artikel
Sprache:eng
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung: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.
ISSN:0021-972X
1945-7197
DOI:10.1210/clinem/dgad666