Deleterious mutation V369M in the mouse GCGR gene causes abnormal plasma amino acid levels indicative of a possible liver & ndash;alpha-cell axis

doi:10.1042/BSR20210758

	Deleterious mutation V369M in the mouse GCGR gene causes abnormal plasma amino acid levels indicative of a possible liver & ndash;alpha-cell axis
	Liu, Qiaofeng 1; Lin, Guangyao 2; Chen, Yan 1; Feng, Wenbo 1; Xu, Yingna 1; Lyu, Jianjun 3; Yang, Dehua 4,5; Wang, Ming-Wei 1,2,4,5,6
刊名	BIOSCIENCE REPORTS
	2021-05-28
卷号	41 期号:6 页码:12
ISSN号	0144-8463
DOI	10.1042/BSR20210758
通讯作者	Yang, Dehua(dhyang@simm.ac.cn) ; Wang, Ming-Wei(mwwang@simm.ac.cn)
英文摘要	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 alpha-cell, thereby establishing a liver-alpha-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 alpha-cell hyperplasia. Here, we investigated the effect of V369M/V368M mutation on glucagon-mediated amino acid metabolism. It was found that GcgrV369M+/+ 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 alpha-cell proliferation and hyperglucagonemia. Glucagon, a peptide hormone secreted by the pancreatic islet alpha-cell, regulates carbohydrate homeostasis and lipid metabolism through its cognate glucagon receptor (GCGR) [1-3]. It releases glucose from the liver by glycogenolysis and stimulates hepatic amino acid uptake [3-5]. It also promotes hepatic amino acids turnover by induction of enzymatic activities via the urea cycle [5,6]. Gcgr knockout or administra
资助项目	National Natural Science Foundation of China[81872915] ; National Natural Science Foundation of China[82073904] ; National Natural Science Foundation of China[81973373] ; National Natural Science Foundation of China[81773792] ; National Science and Technology Major Project of China-Key New Drug Creation and Manufacturing Program[2018ZX09735-001] ; National Science and Technology Major Project of China-Key New Drug Creation and Manufacturing Program[2018ZX09711002-002-005] ; National Key Basic Research Program of China[2018YFA0507000] ; Novo Nordisk-CAS Research Fund grant[NNCAS-2017-1CC]
WOS关键词	ALPHA CELL HYPERPLASIA ; GLUCAGON RECEPTOR ; HYPERGLUCAGONEMIA ; METABOLISM ; PROTEIN
WOS研究方向	Biochemistry & Molecular Biology ; Cell Biology
语种	英语
出版者	PORTLAND PRESS LTD
WOS记录号	WOS:000657302700003
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/297005]
专题	中国科学院上海药物研究所
通讯作者	Yang, Dehua; Wang, Ming-Wei
作者单位	1.Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 3.InnoStar BioTech Nantong Co Ltd, Dept Pathol, Nantong 226133, Peoples R China 4.Chinese Acad Sci, Natl Ctr Drug Screening, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 5.Chinese Acad Sci, CAS Key Lab Receptor Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 6.Fudan Univ, Sch Basic Med Sci, Shanghai 200032, Peoples R China
推荐引用方式 GB/T 7714	Liu, Qiaofeng,Lin, Guangyao,Chen, Yan,et al. Deleterious mutation V369M in the mouse GCGR gene causes abnormal plasma amino acid levels indicative of a possible liver & ndash;alpha-cell axis[J]. BIOSCIENCE REPORTS,2021,41(6):12.
APA	Liu, Qiaofeng.,Lin, Guangyao.,Chen, Yan.,Feng, Wenbo.,Xu, Yingna.,...&Wang, Ming-Wei.(2021).Deleterious mutation V369M in the mouse GCGR gene causes abnormal plasma amino acid levels indicative of a possible liver & ndash;alpha-cell axis.BIOSCIENCE REPORTS,41(6),12.
MLA	Liu, Qiaofeng,et al."Deleterious mutation V369M in the mouse GCGR gene causes abnormal plasma amino acid levels indicative of a possible liver & ndash;alpha-cell axis".BIOSCIENCE REPORTS 41.6(2021):12.