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.
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.
Originalsprog | Engelsk |
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Tidsskrift | Journal of Clinical Endocrinology and Metabolism |
Vol/bind | 109 |
Udgave nummer | 4 |
Sider (fra-til) | 955–967 |
Antal sider | 13 |
ISSN | 0021-972X |
DOI | |
Status | Udgivet - 2024 |