Open AccessDeleterious mutation V369M in the mouse GCGR gene causes abnormal plasma amino acid levels indicative of a possible liver–α-cell axis
Author(s) -
Qiaofeng Liu,
Gonghua Lin,
Yan Chen,
Wenbo Feng,
Yingna Xu,
Jianjun Lyu,
Dehua Yang,
Mingwei Wang
Publication year - 2021
Publication title -
bioscience reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.938
H-Index - 77
eISSN - 1573-4935
pISSN - 0144-8463
DOI - 10.1042/bsr20210758
Subject(s) - hyperglucagonemia , glucagon receptor , glucagon , endocrinology , medicine , amino acid , alpha cell , glucose homeostasis , biology , mutation , metabolism , hypoglycemia , biochemistry , insulin , gene , beta cell , insulin resistance , islet
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 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 α-cell proliferation and hyperglucagonemia.