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

(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...

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Main Authors: 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 Hayashi, Atsushi Suzuki
Format: Article
Language:English
Published: MDPI AG 2022-02-01
Series:Nutrients
Subjects:
Online Access:https://www.mdpi.com/2072-6643/14/5/975
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author 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 Hayashi
Atsushi Suzuki
author_facet 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 Hayashi
Atsushi Suzuki
author_sort Shinji Ueno
collection DOAJ
description (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 <i>Pepck</i> 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.
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spelling doaj.art-550e85e150de4afcbdaf86ee0daed5df2023-11-23T23:32:40ZengMDPI AGNutrients2072-66432022-02-0114597510.3390/nu14050975High Protein Diet Feeding Aggravates Hyperaminoacidemia in Mice Deficient in Proglucagon-Derived PeptidesShinji Ueno0Yusuke Seino1Shihomi Hidaka2Ryuya Maekawa3Yuko Takano4Michiyo Yamamoto5Mika Hori6Kana Yokota7Atsushi Masuda8Tatsuhito Himeno9Shin Tsunekawa10Hideki Kamiya11Jiro Nakamura12Hitoshi Kuwata13Haruki Fujisawa14Megumi Shibata15Takeshi Takayanagi16Yoshihisa Sugimura17Daisuke Yabe18Yoshitaka Hayashi19Atsushi Suzuki20Departments of Endocrinology, Diabetes and Metabolism, Fujita Health University Graduate School of Medicine, Toyoake 470-1192, JapanDepartments of Endocrinology, Diabetes and Metabolism, Fujita Health University Graduate School of Medicine, Toyoake 470-1192, JapanDepartments of Endocrinology, Diabetes and Metabolism, Fujita Health University Graduate School of Medicine, Toyoake 470-1192, JapanDepartment of Endocrinology, Hekinan City Hospital, Hekinan 447-8502, JapanDepartment of Clinical Oncology and Chemotherapy, Nagoya University Hospital, Nagoya 466-8550, JapanDepartment of Endocrinology, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, JapanDepartment of Endocrinology, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, JapanDepartments of Endocrinology, Diabetes and Metabolism, Fujita Health University Graduate School of Medicine, Toyoake 470-1192, JapanDepartments of Endocrinology, Diabetes and Metabolism, Fujita Health University Graduate School of Medicine, Toyoake 470-1192, JapanDivision of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute 480-1195, JapanDivision of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute 480-1195, JapanDivision of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute 480-1195, JapanDivision of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute 480-1195, JapanThe Division of Diabetes, Clinical Nutrition and Endocrinology, Kansai Electric Power Hospital, Osaka 553-0003, JapanDepartments of Endocrinology, Diabetes and Metabolism, Fujita Health University Graduate School of Medicine, Toyoake 470-1192, JapanDepartments of Endocrinology, Diabetes and Metabolism, Fujita Health University Graduate School of Medicine, Toyoake 470-1192, JapanDepartments of Endocrinology, Diabetes and Metabolism, Fujita Health University Graduate School of Medicine, Toyoake 470-1192, JapanDepartments of Endocrinology, Diabetes and Metabolism, Fujita Health University Graduate School of Medicine, Toyoake 470-1192, JapanYutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kobe 650-0047, JapanDepartment of Endocrinology, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, JapanDepartments of Endocrinology, Diabetes and Metabolism, Fujita Health University Graduate School of Medicine, Toyoake 470-1192, Japan(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 <i>Pepck</i> 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.https://www.mdpi.com/2072-6643/14/5/975protein dietglucagonhyperaminoacidemiafood intakehypoglycemia
spellingShingle 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 Hayashi
Atsushi Suzuki
High Protein Diet Feeding Aggravates Hyperaminoacidemia in Mice Deficient in Proglucagon-Derived Peptides
Nutrients
protein diet
glucagon
hyperaminoacidemia
food intake
hypoglycemia
title High Protein Diet Feeding Aggravates Hyperaminoacidemia in Mice Deficient in Proglucagon-Derived Peptides
title_full High Protein Diet Feeding Aggravates Hyperaminoacidemia in Mice Deficient in Proglucagon-Derived Peptides
title_fullStr High Protein Diet Feeding Aggravates Hyperaminoacidemia in Mice Deficient in Proglucagon-Derived Peptides
title_full_unstemmed High Protein Diet Feeding Aggravates Hyperaminoacidemia in Mice Deficient in Proglucagon-Derived Peptides
title_short High Protein Diet Feeding Aggravates Hyperaminoacidemia in Mice Deficient in Proglucagon-Derived Peptides
title_sort high protein diet feeding aggravates hyperaminoacidemia in mice deficient in proglucagon derived peptides
topic protein diet
glucagon
hyperaminoacidemia
food intake
hypoglycemia
url https://www.mdpi.com/2072-6643/14/5/975
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