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Deleterious mutation V369M in the mouse GCGR gene causes abnormal plasma amino acid levels indicative of a possible liver–α-cell axis
Glucagon plays an important role in glucose homeostasis and amino acid metabolism. It regulates plasma amino acid levels which in turn modulate glucagon secretion from the pancreatic α-cell, thereby establishing a liver–α-cell axis described recently. We reported previously that the knock-in mice be...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173527/ https://www.ncbi.nlm.nih.gov/pubmed/34002801 http://dx.doi.org/10.1042/BSR20210758 |
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author | Liu, Qiaofeng Lin, Guangyao Chen, Yan Feng, Wenbo Xu, Yingna Lyu, Jianjun Yang, Dehua Wang, Ming-Wei |
author_facet | Liu, Qiaofeng Lin, Guangyao Chen, Yan Feng, Wenbo Xu, Yingna Lyu, Jianjun Yang, Dehua Wang, Ming-Wei |
author_sort | Liu, Qiaofeng |
collection | PubMed |
description | Glucagon plays an important role in glucose homeostasis and amino acid metabolism. It regulates plasma amino acid levels which in turn modulate glucagon secretion from the pancreatic α-cell, thereby establishing a liver–α-cell axis described recently. We reported previously that the knock-in mice bearing homozygous V369M substitution (equivalent to a naturally occurring mutation V368M in the human glucagon receptor, GCGR) led to hypoglycemia with improved glucose tolerance. They also exhibited hyperglucagonemia, pancreas enlargement and α-cell hyperplasia. Here, we investigated the effect of V369M/V368M mutation on glucagon-mediated amino acid metabolism. It was found that Gcgr(V369M+/+) mice displayed increased plasma amino acid levels in general, but significant accumulation of the ketogenic/glucogenic amino acids was observed in animals fed with a high-fat diet (HFD), resulting in deleterious metabolic consequence characteristic of α-cell proliferation and hyperglucagonemia. |
format | Online Article Text |
id | pubmed-8173527 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-81735272021-06-14 Deleterious mutation V369M in the mouse GCGR gene causes abnormal plasma amino acid levels indicative of a possible liver–α-cell axis Liu, Qiaofeng Lin, Guangyao Chen, Yan Feng, Wenbo Xu, Yingna Lyu, Jianjun Yang, Dehua Wang, Ming-Wei Biosci Rep Diabetes & Metabolic Disorders Glucagon plays an important role in glucose homeostasis and amino acid metabolism. It regulates plasma amino acid levels which in turn modulate glucagon secretion from the pancreatic α-cell, thereby establishing a liver–α-cell axis described recently. We reported previously that the knock-in mice bearing homozygous V369M substitution (equivalent to a naturally occurring mutation V368M in the human glucagon receptor, GCGR) led to hypoglycemia with improved glucose tolerance. They also exhibited hyperglucagonemia, pancreas enlargement and α-cell hyperplasia. Here, we investigated the effect of V369M/V368M mutation on glucagon-mediated amino acid metabolism. It was found that Gcgr(V369M+/+) mice displayed increased plasma amino acid levels in general, but significant accumulation of the ketogenic/glucogenic amino acids was observed in animals fed with a high-fat diet (HFD), resulting in deleterious metabolic consequence characteristic of α-cell proliferation and hyperglucagonemia. Portland Press Ltd. 2021-06-02 /pmc/articles/PMC8173527/ /pubmed/34002801 http://dx.doi.org/10.1042/BSR20210758 Text en © 2021 The Author(s). https://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Diabetes & Metabolic Disorders Liu, Qiaofeng Lin, Guangyao Chen, Yan Feng, Wenbo Xu, Yingna Lyu, Jianjun Yang, Dehua Wang, Ming-Wei Deleterious mutation V369M in the mouse GCGR gene causes abnormal plasma amino acid levels indicative of a possible liver–α-cell axis |
title | Deleterious mutation V369M in the mouse GCGR gene causes abnormal plasma amino acid levels indicative of a possible liver–α-cell axis |
title_full | Deleterious mutation V369M in the mouse GCGR gene causes abnormal plasma amino acid levels indicative of a possible liver–α-cell axis |
title_fullStr | Deleterious mutation V369M in the mouse GCGR gene causes abnormal plasma amino acid levels indicative of a possible liver–α-cell axis |
title_full_unstemmed | Deleterious mutation V369M in the mouse GCGR gene causes abnormal plasma amino acid levels indicative of a possible liver–α-cell axis |
title_short | Deleterious mutation V369M in the mouse GCGR gene causes abnormal plasma amino acid levels indicative of a possible liver–α-cell axis |
title_sort | deleterious mutation v369m in the mouse gcgr gene causes abnormal plasma amino acid levels indicative of a possible liver–α-cell axis |
topic | Diabetes & Metabolic Disorders |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173527/ https://www.ncbi.nlm.nih.gov/pubmed/34002801 http://dx.doi.org/10.1042/BSR20210758 |
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