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Absence of PNET formation and normal longevity in a mouse model of Mahvash disease

文献类型：期刊论文

作者Xu, Yingna8; Liu, Qiaofeng7; Chen, Chuan-Wei6; Wang, Qiuying5; Du, Tianyuan5; Yu, Run4; Zhou, Qingtong6; Yang, Dehua3,5,6; Wang, Ming-Wei1,2,6,8
刊名HELIYON
出版日期2024-08-15
卷号10期号:15页码:13
关键词Glucagon Glucagon receptor Amino acid Metabolism Mahvash disease
DOI10.1016/j.heliyon.2024.e35362
通讯作者Yang, Dehua(dhyang@simm.ac.cn) ; Wang, Ming-Wei(mwwang@simm.ac.cn)
英文摘要Mahvash disease, a rare autosomal recessive metabolic disorder characterized by biallelic loss-offunction mutations in the glucagon receptor gene (GCGR), induces significant pancreatic hyperglucagonemia, resulting in alpha-cell hyperplasia and occasional hypoglycemia. Utilizing CRISPR-Cas9 technology, we engineered a mouse model, designated as GcgrV369M/V369M, harboring a homozygous V369M substitution in the glucagon receptor (GCGR). Although wildtype (WT) and GcgrV369M/V369M mice exhibited no discernible difference in appearance or weight, adult GcgrV369M/V369M mice, approximately 12 months of age, displayed a notable decrease in fasting blood glucose levels and elevated the levels of cholesterol and low-density lipoprotein-cholesterol. Moreover, plasma amino acid levels such as alanine (Ala), proline (Pro) and arginine (Arg) were elevated in GcgrV369M/V369M mice contributing to alpha-cell proliferation and hyperglucagonemia. Despite sustained alpha-cell hyperplasia and increased circulating glucagon levels in GcgrV369M/V369M mice, metabolic disparities between the two groups gradually waned with age accompanied by a reduction in alpha-cell hyperplasia. Throughout the lifespan of the mice (up to approximately 30 months), pancreatic neuroendocrine tumors (PNETs) did not manifest. This prolonged observation of metabolic alterations in GcgrV369M/V369M mice furnishes valuable insights for a deeper comprehension of mild Mahvash disease in humans.
WOS关键词ALPHA CELL HYPERPLASIA ; GLUCAGON RECEPTOR ; BLOOD-GLUCOSE ; HYPERGLUCAGONEMIA ; GENES
资助项目National Natural Science Foundation of China[82273961] ; National Natural Science Foundation of China[81872915] ; National Natural Science Foundation of China[82073904] ; National Natural Science Foundation of China[82273985] ; National Natural Science Foundation of China[81973373] ; National Natural Science Foundation of China[82121005] ; National Science & Technology Major Project of China-Key New Drug Creation and Manufacturing Program[2018ZX09735-001] ; National Science & Technology Major Project of China-Key New Drug Creation and Manufacturing Program[2018ZX09711002-002-005] ; STI2030-Major Project[2021ZD0203400] ; National Key Basic Research Program of China[2023YFA1800804] ; Hainan Provincial Major Science and Technology Project[ZDKJ2021028] ; Program of Shanghai Academic/Technology Research Leader[23XD1400900] ; Shanghai Municipality Science and Technology Development Fund[21JC1401600]
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:001286664300001
出版者CELL PRESS
源URL[http://119.78.100.183/handle/2S10ELR8/312715]  
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.Hainan Med Univ, Engn Res Ctr Trop Med Innovat & Transformat, Sch Pharm, Minist Educ, Haikou 570228, Peoples R China
2.Univ Tokyo, Sch Sci, Dept Chem, Tokyo 1130033, Japan
3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Chem Biol, Shanghai 201203, Peoples R China
4.UCLA, Div Endocrinol Diabet & Metab, David Geffen Sch Med, Los Angeles, CA 90095 USA
5.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China
6.Res Ctr Deepsea Bioresources, Sanya 572025, Hainan, Peoples R China
7.Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China
8.Fudan Univ, Sch Basic Med Sci, Dept Pharmacol, Shanghai 200032, Peoples R China
推荐引用方式
GB/T 7714		 Xu, Yingna,Liu, Qiaofeng,Chen, Chuan-Wei,et al. Absence of PNET formation and normal longevity in a mouse model of Mahvash disease[J]. HELIYON,2024,10(15):13.
APA Xu, Yingna.,Liu, Qiaofeng.,Chen, Chuan-Wei.,Wang, Qiuying.,Du, Tianyuan.,...&Wang, Ming-Wei.(2024).Absence of PNET formation and normal longevity in a mouse model of Mahvash disease.HELIYON,10(15),13.
MLA Xu, Yingna,et al."Absence of PNET formation and normal longevity in a mouse model of Mahvash disease".HELIYON 10.15(2024):13.

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来源：上海药物研究所

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