What question did this study set out to answer?

This research investigates how circulating concentrations of amino acids, glucose, and insulin contribute to glucagon secretion, especially in obesity and prediabetes.

June 10, 2026

1327-OR: The Contribution of Circulating Amino Acid, Glucose and Insulin Concentrations to Glucagon Secretion

Key Points

This research investigates how circulating concentrations of amino acids, glucose, and insulin contribute to glucagon secretion, especially in obesity and prediabetes.
Lean (BMI: 23 ± 0.5 kg/m2, n = 10) and obese (BMI: 31 ± 0.6 kg/m2, n = 16) subjects were studied after an overnight fast.
Subjects underwent two study days with either saline or amino acid infusion to evaluate glucagon secretion rates.
Amino acids were measured by mass spectrometry at defined intervals during the study.
Insulin levels rose, while glucagon levels showed an inverse-exponential suppression during both study days.
Amino acid infusion elevated 15 specific amino acids compared to saline, impacting glucagon responses.
Arginine and histidine concentrations, adjusted for weight, correlated with a rise in G50, indicating impaired glucagon suppression in obese subjects (R2 = 0.45, p = 2.6 x 10-5).

Abstract

Introduction and Objective: Obesity and prediabetes are characterized by abnormal glucagon response to glucose and amino acids (AA). Elevated AA concentrations, seen in these states, are associated with increased risk of type 2 diabetes. The relative contributions of AA, glucose and insulin to glucagon secretion is unknown. Methods: Lean (BMI: 23 ± 0.5 kg/m2, n = 10) and obese (BMI 31 ± 0.6 kg/m2, n = 16) subjects were studied on two occasions in random order after an overnight fast using a graded glucose infusion. On one occasion saline was infused (Saline Day) and on the other, an AA mixture Clinisol 15%, 0.003ml/kg/min; Baxter, Healthcare, Deerfield, IL) AA day. The glucagon secretion rate (GSR) was derived from peripheral glucagon concentrations using a mathematical model, which also provided G50 - the change in glucose required to reduce GSR by 50%. AA and their metabolites (n = 42) were measured by mass spectrometry at 0, 120 and 240 mins. Results: During both study days, we observed a progressive rise in insulin and an inverse-exponential suppression of glucagon. AA infusion produced elevation of 15 AA compared to the saline day. We had previously observed that AA stimulation of glucagon secretion led to impaired suppression by hyperglycemia in obese subjects, resulting in an increased G50 that correlated with body weight (R2 = 0.15, p = 9.9 x 10-3). Examination of the relationship of G50 with AA concentrations suggests that when adjusted for weight, arginine and histidine concentrations are correlated with rise of G50 (R2 = 0.45, p = 2.6 x 10-5). Neither glucose nor insulin concentrations observed at peak AA concentrations altered this relationship. Conclusion: Circulating concentrations of arginine and histidine modulate α-cell function. This effect is more marked as weight increases and occurs independent of changes to glucose and insulin concentrations. Disclosure S. Mohan: None. F. Boscolo: None. H.E. Christie: None. A. Egan: None. C. Dalla Man: Other - Webinar provider; Ended; Sanofi. Other - Joint research project; Current; Sanofi-Aventis Deutschland GmbH. A. Vella: Advisory Panel; Ended; Boehringer Ingelheim International GmbH. Advisory Panel; Current; Rezolute. Research Support; Current; Dexcom, Inc. Advisory Panel; Current; Neurotronic, Amylx. Funding National Institutes of Health (DK116723)

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Cite This Study

MOHAN et al. (Mon,) studied this question.

synapsesocial.com/papers/6a28ff956f82f25be989c663 https://doi.org/https://doi.org/10.2337/db26-1327-or

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