The effect of exogenous glucagon on circulating amino acids in individuals with and without type 2 diabetes and obesity.

OBJECTIVE: In obesity and type 2 diabetes, hyperglucagonaemia may be caused by elevated levels of glucagonotropic amino acids due to hepatic glucagon resistance at the level of amino acid turnover. Here, we investigated the effect of exogenous glucagon on circulating amino acids in obese and non-obese individuals with and without type 2 diabetes.

DESIGN: This was a post-hoc analysis in a glucagon infusion study performed in individuals with type 2 diabetes (n=16) and in age, sex, and body mass index (BMI)-matched control individuals without diabetes (n=16). Each group comprised two subgroups of 8 individuals with and without obesity, respectively.

METHODS: All participants received a 1-hour glucagon infusion (4 ng/kg/min) in the overnight fasted state. Plasma amino acid concentrations were measured with frequent intervals.

RESULTS: Compared to the Control subgroup without obesity, baseline total amino acid levels were elevated in the Control subgroup with obesity and in the Type 2 diabetes subgroup without obesity. In all subgroups, amino acid levels decreased by up to 20% in response to glucagon infusion, which resulted in high physiological steady state glucagon levels (mean concentration: 74 pmol/L, 95% CI [68;79] pmol/L)). Following correction for multiple testing, no intergroup differences in changes in amino acid levels reached significance.

CONCLUSION: Obesity and type 2 diabetes status was associated with elevated fasting levels of total amino acids. The glucagon infusion decreased circulating amino acid levels similarly in all subgroups, without significant differences in the response to exogenous glucagon between individuals with and without obesity and type 2 diabetes.