Departments of Endocrinology, Diabetes and Metabolism, Fujita Health University Graduate School of Medicine, Toyoake 470-1192, Japan.
Department of Endocrinology, Hekinan City Hospital, Hekinan 447-8502, Japan.
Nutrients. 2022 Feb 25;14(5):975. doi: 10.3390/nu14050975.
(1) Background: Protein stimulates the secretion of glucagon (GCG), which can affect glucose metabolism. This study aimed to analyze the metabolic effect of a high-protein diet (HPD) in the presence or absence of proglucagon-derived peptides, including GCG and GLP-1. (2) Methods: The response to HPD feeding for 7 days was analyzed in mice deficient in proglucagon-derived peptides (GCGKO). (3) Results: In both control and GCGKO mice, food intake and body weight decreased with HPD and intestinal expression of increased. HPD also decreased plasma FGF21 levels, regardless of the presence of proglucagon-derived peptides. In control mice, HPD increased the hepatic expression of enzymes involved in amino acid metabolism without the elevation of plasma amino acid levels, except branched-chain amino acids. On the other hand, HPD-induced changes in the hepatic gene expression were attenuated in GCGKO mice, resulting in marked hyperaminoacidemia with lower blood glucose levels; the plasma concentration of glutamine exceeded that of glucose in HPD-fed GCGKO mice. (4) Conclusions: Increased plasma amino acid levels are a common feature in animal models with blocked GCG activity, and our results underscore that GCG plays essential roles in the homeostasis of amino acid metabolism in response to altered protein intake.
(1) 背景：蛋白质可刺激胰高血糖素（GCG）的分泌，从而影响葡萄糖代谢。本研究旨在分析高蛋白饮食（HPD）在存在或不存在胰高血糖素原衍生肽（包括 GCG 和 GLP-1）时的代谢效应。
(2) 方法：分析了缺乏胰高血糖素原衍生肽的小鼠（GCGKO）接受 HPD 喂养 7 天的反应。
(3) 结果：在对照和 GCGKO 小鼠中，HPD 喂养都会导致食物摄入和体重下降，同时肠道表达增加。无论是否存在胰高血糖素原衍生肽，HPD 都会降低 FGF21 水平。在对照小鼠中，HPD 增加了参与氨基酸代谢的肝脏酶的表达，而不会引起血浆氨基酸水平升高，除了支链氨基酸。另一方面，HPD 诱导的肝基因表达变化在 GCGKO 小鼠中减弱，导致显著的高氨基酸血症和较低的血糖水平；HPD 喂养的 GCGKO 小鼠的血浆谷氨酰胺浓度超过血糖浓度。
(4) 结论：在 GCG 活性受阻的动物模型中，血浆氨基酸水平升高是一个共同特征，我们的结果强调了 GCG 在应对蛋白质摄入改变时对氨基酸代谢平衡的重要作用。
