G protein-coupled receptor 151 regulates glucose metabolism and hepatic gluconeogenesis.
G protein-coupled receptor 151 regulates glucose metabolism and hepatic gluconeogenesis.
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DOI:
10.1038/s41467-022-35069-9
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发表时间:
2022-12-01
影响因子:
16.6
通讯作者:
Knowles, Joshua W.
中科院分区:
文献类型:
--
作者:
Bielczyk-Maczynska, Ewa;Zhao, Meng;Zushin, Peter-James H.;Schnurr, Theresia M.;Kim, Hyun-Jung;Li, Jiehan;Nallagatla, Pratima;Sangwung, Panjamaporn;Park, Chong Y.;Cornn, Cameron;Stahl, Andreas;Svensson, Katrin J.;Knowles, Joshua W.
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. Rare variants in the G-protein coupled receptor 151 (GPR151) gene in humans are associated with lower odds ratio for type 2 diabetes, but the mechanism behind this association has remained elusive. Here, the authors show that GPR151 regulates the process of hepatic gluconeogenesis and affects whole-body glucose metabolism.
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影响因子:
4.5
作者:
通讯作者:
--
影响因子:
15.9
作者:
Meyer, C;Stumvoll, M;Gerich, J
通讯作者:
Gerich, J
影响因子:
14.9
作者:
Kreft L;Soete A;Hulpiau P;Botzki A;Saeys Y;De Bleser P
通讯作者:
De Bleser P
影响因子:
56.9
作者:
Akbari, Parsa;Gilani, Ankit;Sosina, Olukayode;Kosmicki, Jack A.;Khrimian, Lori;Fang, Yi-Ya;Persaud, Trikaldarshi;Garcia, Victor;Sun, Dylan;Li, Alexander;Mbatchou, Joelle;Locke, Adam E.;Benner, Christian;Verweij, Niek;Lin, Nan;Hossain, Sakib;Agostinucci, Kevin;Pascale, Jonathan, V;Dirice, Ercument;Dunn, Michael;Kraus, William E.;Shah, Svati H.;Chen, Yii-Der, I;Rotter, Jerome, I;Rader, Daniel J.;Melander, Olle;Still, Christopher D.;Mirshahi, Tooraj;Carey, David J.;Berumen-Campos, Jaime;Kuri-Morales, Pablo;Alegre-Diaz, Jesus;Torres, Jason M.;Emberson, Jonathan R.;Collins, Rory;Balasubramanian, Suganthi;Hawes, Alicia;Jones, Marcus;Zambrowicz, Brian;Murphy, Andrew J.;Paulding, Charles;Coppola, Giovanni;Overton, John D.;Reid, Jeffrey G.;Shuldiner, Alan R.;Cantor, Michael;Kang, Hyun M.;Abecasis, Goncalo R.;Karalis, Katia;Economides, Aris N.;Marchini, Jonathan;Yancopoulos, George D.;Sleeman, Mark W.;Altarejos, Judith;Della Gatta, Giusy;Tapia-Conyer, Roberto;Schwartzman, Michal L.;Baras, Aris;Ferreira, Manuel A. R.;Lotta, Luca A.
通讯作者:
Lotta, Luca A.
影响因子:
30.8
作者:
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通讯作者:
Meta-Analysis of Glucose and Insulin-related Traits Consortium (MAGIC)