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-matched control individuals without diabetes (n = 16). Each group comprised two subgroups of eight individuals with and without obesity, respectively.

Methods

All participants received a 1-h 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.

Significance statement

The hormone glucagon stimulates glucose production from the liver, which may promote hyperglycaemia if glucagon levels are abnormally elevated, as is often seen in type 2 diabetes and obesity. Glucagon levels are closely linked to, and influenced by, the levels of circulating amino acids. To further investigate this link, we measured amino acid levels in individuals with and without obesity and type 2 diabetes before and during an infusion of glucagon. We found that circulating amino acid levels were higher in type 2 diabetes and obesity, and that glucagon infusion decreased amino acid levels in both individuals with and without type 2 diabetes and obesity. The study adds novel information to the link between circulating levels of glucagon and amino acids.

中文翻译：

---

外源性胰高血糖素对患有和不患有 2 型糖尿病和肥胖症的个体循环氨基酸的影响

客观的

在肥胖和2型糖尿病中，高胰高血糖素血症可能是由于氨基酸周转水平上的肝胰高血糖素抵抗导致促胰高血糖素氨基酸水平升高引起的。在此，我们研究了外源性胰高血糖素对患有或不患有 2 型糖尿病的肥胖和非肥胖个体的循环氨基酸的影响。

设计

这是对 2 型糖尿病患者 ( n = 16) 和年龄、性别和体重指数匹配的无糖尿病对照个体 ( n = 16) 进行的胰高血糖素输注研究的事后分析。每组由两个亚组组成，每个亚组分别由八名患有肥胖症和不患有肥胖症的人组成。

方法

所有参与者在过夜禁食状态下接受 1 小时胰高血糖素输注（4 ng/kg/min）。频繁地测量血浆氨基酸浓度。

结果

与没有肥胖的对照亚组相比，肥胖对照亚组和没有肥胖的2型糖尿病亚组的基线总氨基酸水平升高。在所有亚组中，胰高血糖素输注后氨基酸水平下降高达 20%，从而导致生理稳态胰高血糖素水平较高（平均浓度：74 pmol/L，95% CI [68;79] pmol/L） 。经过多次测试校正后，氨基酸水平变化的组间差异没有达到显着性。

结论

肥胖和 2 型糖尿病状态与空腹总氨基酸水平升高相关。在所有亚组中，胰高血糖素输注均类似地降低了循环氨基酸水平，患有和不患有肥胖和2型糖尿病的个体对外源性胰高血糖素的反应没有显着差异。

意义陈述

胰高血糖素激素会刺激肝脏产生葡萄糖，如果胰高血糖素水平异常升高，可能会导致高血糖，这在 2 型糖尿病和肥胖症中很常见。胰高血糖素水平与循环氨基酸水平密切相关并受其影响。为了进一步研究这种联系，我们在注射胰高血糖素之前和期间测量了患有或不患有肥胖和 2 型糖尿病的个体的氨基酸水平。我们发现 2 型糖尿病和肥胖症患者的循环氨基酸水平较高，而胰高血糖素输注可降低患有和不患有 2 型糖尿病和肥胖症的个体的氨基酸水平。该研究为胰高血糖素和氨基酸循环水平之间的联系提供了新的信息。