High Protein Diet Feeding Aggravates Hyperaminoacidemia in Mice Deficient in Proglucagon-Derived Peptides

Shinji Ueno, Yusuke Seino, Shihomi Hidaka, Ryuya Maekawa, Yuko Takano, Michiyo Yamamoto, Mika Hori, Kana Yokota, Atsushi Masuda, Tatsuhito Himeno, Shin Tsunekawa, Hideki Kamiya, Jiro Nakamura, Hitoshi Kuwata, Haruki Fujisawa, Megumi Shibata, Takeshi Takayanagi, Yoshihisa Sugimura, Daisuke Yabe, Yoshitaka HayashiAtsushi Suzuki

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


(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 Pepck 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.

Original languageEnglish
Article number975
Issue number5
Publication statusPublished - 01-03-2022

All Science Journal Classification (ASJC) codes

  • Food Science
  • Nutrition and Dietetics


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