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G protein-coupled receptor 151 regulates glucose metabolism and hepatic gluconeogenesis
Nature Communications ( IF 16.6 ) Pub Date : 2022-12-01 , DOI: 10.1038/s41467-022-35069-9
Ewa Bielczyk-Maczynska 1, 2, 3 , Meng Zhao 2, 3, 4 , Peter-James H Zushin 5 , Theresia M Schnurr 1, 2, 3 , Hyun-Jung Kim 1 , Jiehan Li 1, 2, 3 , Pratima Nallagatla 6 , Panjamaporn Sangwung 1, 2, 3 , Chong Y Park 1, 2, 3 , Cameron Cornn 1 , Andreas Stahl 5 , Katrin J Svensson 2, 3, 4 , Joshua W Knowles 1, 2, 3, 7
Affiliation  

Human genetics has been instrumental in identification of genetic variants linked to type 2 diabetes. Recently a rare, putative loss-of-function mutation in the orphan G-protein coupled receptor 151 (GPR151) was found to be associated with lower odds ratio for type 2 diabetes, but the mechanism behind this association has remained elusive. Here we show that Gpr151 is a fasting- and glucagon-responsive hepatic gene which regulates hepatic gluconeogenesis. Gpr151 ablation in mice leads to suppression of hepatic gluconeogenesis genes and reduced hepatic glucose production in response to pyruvate. Importantly, the restoration of hepatic Gpr151 levels in the Gpr151 knockout mice reverses the reduced hepatic glucose production. In this work, we establish a previously unknown role of Gpr151 in the liver that provides an explanation to the lowered type 2 diabetes risk in individuals with nonsynonymous mutations in GPR151.



中文翻译:

G 蛋白偶联受体 151 调节葡萄糖代谢和肝糖异生

人类遗传学有助于鉴定与 2 型糖尿病相关的遗传变异。最近发现孤儿 G 蛋白偶联受体 151 ( GPR151 ) 中一种罕见的假定功能丧失突变与 2 型糖尿病的较低比值比相关,但这种关联背后的机制仍然难以捉摸。在这里,我们显示Gpr151是一种禁食和胰高血糖素反应性肝基因,可调节肝糖异生。小鼠中的Gpr151消融导致肝糖异生基因的抑制和对丙酮酸的反应减少肝葡萄糖的产生。重要的是,Gpr151 中肝脏Gpr151水平的恢复基因敲除小鼠逆转了肝脏葡萄糖生成的减少。在这项工作中,我们确定了Gpr151在肝脏中以前未知的作用,该作用解释了具有GPR151非同义突变的个体 2 型糖尿病风险降低的原因。

更新日期:2022-12-01
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