The effect of a high protein diet on skeletal muscle function-interaction between organs mediated by glucagon-

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K11608
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Fujita Health University
• Principal Investigator: Seino Yusuke 藤田医科大学, 医学部, 准教授 (80534833)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: グルカゴン / アミノ酸 / 肝臓 / 筋肉 / 高蛋白質食 / 脂肪組織 / プログルカゴン

Outline of Final Research Achievements

Mice fed a high-protein diet for one week showed decreased adipose tissue weight and skeletal muscle mass due to reduced food intake in comparison with mice fed normal chow. In mice fed a high-protein diet, glucagon secretion was promoted and amino acid metabolism in the liver was enhanced, so plasma amino acid concentrations except for branched-chain amino acids were not elevated in comparison with mice fed a normal diet. On the other hand, glucagon-deficient (GCGKO) mice, which display hyperaminoacidemia, showed increased lean mass, muscle fiber hypertrophy caused by enhancement of the IGF1-Akt signal, and a decreased ratio of type IIA fibers, which are mostly slow-twitch, and an increased ratio of type IIB fibers, which are mostly fast-twitch, in the tibialis anterior compared to control mice. Accordingly, GCGKO mice show increased grip strength.

Free Research Field

内分泌・代謝・栄養学

Academic Significance and Societal Importance of the Research Achievements

高齢者糖尿病ではサルコペニアの有病率が高く、蛋白質摂取量を多くすることが推奨されている。本研究で(1) 蛋白質摂取量が多くてもグルカゴン分泌・作用の亢進のため筋合成にはあまり効率ではないこと(2)糖尿病治療として注目されているグルカゴンの作用遮断は、血糖値改善のみならず血中アミノ酸濃度の上昇を起こし、老化とともに問題となる筋肉量、特に速筋量の減少を予防できる可能性があることが明らかとなり、これらの結果より蛋白質摂取時はグルカゴン作用を減弱するような薬剤の併用にて高齢者糖尿病の筋肉委縮を軽減できると考えられる。