GPRC6A Mediates Glucose and Amino Acid Homeostasis in Mice

GPRC6A, an important member of the G-protein-coupled receptor superfamily, has been widely studied in body health maintenance and related diseases. However, it is still controversial whether GPRC6A plays a vital role in glucose homeostasis, and the role of GPRC6A on amino acid homeostasis has not be...

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Main Authors: Yumin He, Jingyun Su, Hongrui Gao, Jianzhong Li, Zemeng Feng, Yulong Yin
Format: Article
Language:English
Published: MDPI AG 2022-08-01
Series:Metabolites
Subjects:
Online Access:https://www.mdpi.com/2218-1989/12/8/740
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author Yumin He
Jingyun Su
Hongrui Gao
Jianzhong Li
Zemeng Feng
Yulong Yin
author_facet Yumin He
Jingyun Su
Hongrui Gao
Jianzhong Li
Zemeng Feng
Yulong Yin
author_sort Yumin He
collection DOAJ
description GPRC6A, an important member of the G-protein-coupled receptor superfamily, has been widely studied in body health maintenance and related diseases. However, it is still controversial whether GPRC6A plays a vital role in glucose homeostasis, and the role of GPRC6A on amino acid homeostasis has not been reported. In this study, GPRC6A was knocked out in C57BL6 mice, and we found that GPRC6A plays an important role in the glucose metabolism, mainly affecting the glucose clearance capacity and gluconeogenesis in mice. GPRC6A plays an important role in maintaining amino acid homeostasis under dietary restrictions, and this may be realized by participating in the regulation of autophagy. Since a large amount of amino acid is lost from urine in aged GPRC6A<sup>−/−</sup> mice, it is possible that GPRC6A regulates amino acid homeostasis by affecting the integrity of tissue structure. GPRC6A is involved in the regulation of mTORC1 activation but is not necessary for mTORC1 activation under sufficient nutritional supply. In the absence of exogenous amino acids, the loss of GPRC6A induces the GCN2 pathway activation and excessive autophagy of cells, leading to the overactivation of mTORC1, which may be detrimental to body health and cell survival. In summary, this study provides a theoretical and experimental basis for the metabolic process of GPRC6A in body growth and health.
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spelling doaj.art-94e41595867d4bc6a766c39e154478c12023-11-30T21:58:20ZengMDPI AGMetabolites2218-19892022-08-0112874010.3390/metabo12080740GPRC6A Mediates Glucose and Amino Acid Homeostasis in MiceYumin He0Jingyun Su1Hongrui Gao2Jianzhong Li3Zemeng Feng4Yulong Yin5Animal Nutrition and Human Health Laboratory, College of Life Sciences, Hunan Normal University, Changsha 410081, ChinaAnimal Nutrition and Human Health Laboratory, College of Life Sciences, Hunan Normal University, Changsha 410081, ChinaHunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, Key Laboratory of Agro-Ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Hunan Provincial Engineering Research Canter for Healthy Livestock and Poultry Production, Scientific Observational and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Changsha 410125, ChinaAnimal Nutrition and Human Health Laboratory, College of Life Sciences, Hunan Normal University, Changsha 410081, ChinaHunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, Key Laboratory of Agro-Ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Hunan Provincial Engineering Research Canter for Healthy Livestock and Poultry Production, Scientific Observational and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Changsha 410125, ChinaAnimal Nutrition and Human Health Laboratory, College of Life Sciences, Hunan Normal University, Changsha 410081, ChinaGPRC6A, an important member of the G-protein-coupled receptor superfamily, has been widely studied in body health maintenance and related diseases. However, it is still controversial whether GPRC6A plays a vital role in glucose homeostasis, and the role of GPRC6A on amino acid homeostasis has not been reported. In this study, GPRC6A was knocked out in C57BL6 mice, and we found that GPRC6A plays an important role in the glucose metabolism, mainly affecting the glucose clearance capacity and gluconeogenesis in mice. GPRC6A plays an important role in maintaining amino acid homeostasis under dietary restrictions, and this may be realized by participating in the regulation of autophagy. Since a large amount of amino acid is lost from urine in aged GPRC6A<sup>−/−</sup> mice, it is possible that GPRC6A regulates amino acid homeostasis by affecting the integrity of tissue structure. GPRC6A is involved in the regulation of mTORC1 activation but is not necessary for mTORC1 activation under sufficient nutritional supply. In the absence of exogenous amino acids, the loss of GPRC6A induces the GCN2 pathway activation and excessive autophagy of cells, leading to the overactivation of mTORC1, which may be detrimental to body health and cell survival. In summary, this study provides a theoretical and experimental basis for the metabolic process of GPRC6A in body growth and health.https://www.mdpi.com/2218-1989/12/8/740glucoseamino acidsGPRC6AmTORC1autophagy
spellingShingle Yumin He
Jingyun Su
Hongrui Gao
Jianzhong Li
Zemeng Feng
Yulong Yin
GPRC6A Mediates Glucose and Amino Acid Homeostasis in Mice
Metabolites
glucose
amino acids
GPRC6A
mTORC1
autophagy
title GPRC6A Mediates Glucose and Amino Acid Homeostasis in Mice
title_full GPRC6A Mediates Glucose and Amino Acid Homeostasis in Mice
title_fullStr GPRC6A Mediates Glucose and Amino Acid Homeostasis in Mice
title_full_unstemmed GPRC6A Mediates Glucose and Amino Acid Homeostasis in Mice
title_short GPRC6A Mediates Glucose and Amino Acid Homeostasis in Mice
title_sort gprc6a mediates glucose and amino acid homeostasis in mice
topic glucose
amino acids
GPRC6A
mTORC1
autophagy
url https://www.mdpi.com/2218-1989/12/8/740
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AT jianzhongli gprc6amediatesglucoseandaminoacidhomeostasisinmice
AT zemengfeng gprc6amediatesglucoseandaminoacidhomeostasisinmice
AT yulongyin gprc6amediatesglucoseandaminoacidhomeostasisinmice