G protein-coupled receptor 151 regulates glucose metabolism and hepatic gluconeogenesis

Ewa Bielczyk-Maczynska, Meng Zhao, Peter James H. Zushin, Theresia M. Schnurr, Hyun Jung Kim, Jiehan Li, Pratima Nallagatla, Panjamaporn Sangwung, Chong Y. Park, Cameron Cornn, Andreas Stahl, Katrin J. Svensson, Joshua W. Knowles

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2 Scopus citations


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.

Original languageEnglish (US)
Article number7408
JournalNature communications
Issue number1
StatePublished - Dec 2022
Externally publishedYes

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