Deleterious mutation V369M in the mouse GCGR gene causes abnormal plasma amino acid levels indicative of a possible liver–α-cell axis. Issue 6 (25th June 2021)

• Record Type: Journal Article
• Authors: Liu, Qiaofeng; Lin, Guangyao; Chen, Yan; Feng, Wenbo; Xu, Yingna; Lyu, Jianjun; Yang, Dehua; Wang, Ming-Wei
• Is Part Of: Bioscience reports. Volume 41:Issue 6(2021)
• Publication Date: 2021-06-25
• Subjects: glucagon receptor -- mouse model -- mutation -- proliferation -- V369M; Molecular biology -- Periodicals; Cytology -- Periodicals; 572.8
• DOI: 10.1042/BSR20210758
• Languages: English
• ISSNs: 0144-8463

Abstract

Abstract: 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.