Signs of Glucagon Resistance After a Two-Week Hypercaloric Diet Intervention
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Signs of Glucagon Resistance After a Two-Week Hypercaloric Diet Intervention. / Suppli, Malte Palm; Høgedal, Astrid; Bagger, Jonatan Ising; Chabanova, Elizaveta; van Hall, Gerrit; Forman, Julie Lyng; Christensen, Mikkel Bring; Wewer Albrechtsen, Nicolai Jacob; Holst, Jens Juul; Knop, Filip Krag.
I: Journal of Clinical Endocrinology and Metabolism, Bind 109, Nr. 4, 2024, s. 955–967.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Signs of Glucagon Resistance After a Two-Week Hypercaloric Diet Intervention
AU - Suppli, Malte Palm
AU - Høgedal, Astrid
AU - Bagger, Jonatan Ising
AU - Chabanova, Elizaveta
AU - van Hall, Gerrit
AU - Forman, Julie Lyng
AU - Christensen, Mikkel Bring
AU - Wewer Albrechtsen, Nicolai Jacob
AU - Holst, Jens Juul
AU - Knop, Filip Krag
N1 - © 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.
PY - 2024
Y1 - 2024
N2 - 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 two 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 eight 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 < 0.01). 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 = 0.015) 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 = 0.016) 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.
AB - 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 two 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 eight 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 < 0.01). 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 = 0.015) 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 = 0.016) 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.
U2 - 10.1210/clinem/dgad666
DO - 10.1210/clinem/dgad666
M3 - Journal article
C2 - 37967235
VL - 109
SP - 955
EP - 967
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 4
ER -
ID: 379726221