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The following is a summary of “Signs of Glucagon Resistance After a 2-Week Hypercaloric Diet Intervention,” published in the April 2024 issue of Endocrinology by Suppli, et al.
Hyperglucagonemia is commonly observed in obese individuals and contributes to the hyperglycemia seen in patients with type 2 diabetes. This phenomenon may result from hepatic glucagon resistance induced by steatosis, leading to impaired hepatic amino acid turnover and subsequent elevations in circulating glucagonotropic amino acids. For a study, researchers sought to assess whether glucagon resistance could be induced in healthy individuals through a hypercaloric diet intervention designed to increase hepatic fat content.
About 20 healthy male participants were recruited to follow a hypercaloric diet and sedentary lifestyle for 2 weeks. During glucagon infusion, amino acid concentrations were evaluated using a pancreatic clamp with somatostatin and basal insulin. The reversibility of any metabolic changes was assessed 8 weeks after the intervention. Hepatic steatosis was evaluated by magnetic resonance spectroscopy.
The intervention resulted in a significant increase in hepatic fat content (382% [206%; 705%], P < .01). Glucagon infusion led to a decrease in total amino acid concentration 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 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.
The study’s findings are significant, suggesting that short-term unhealthy behavior leading to increased hepatic fat content induces reversible resistance to the effect of glucagon on amino acid concentrations in healthy individuals. This phenomenon may help explain the hyperglucagonemia observed in obesity and diabetes, underscoring the importance of understanding glucagon resistance in metabolic disorders.
Reference: academic.oup.com/jcem/article-abstract/109/4/955/7423951
