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Although the mechanism of T2DM is not yet fully known, inflammation and insulin resistance play a central role in the pathogenesis of T2DM. G protein\u2010coupled receptors (GPCRs) are involved in endocrine and metabolic processes as well as many other physiological processes. GPR50 (G protein\u2010coupled receptor 50) is an orphan GPCR that shares the highest sequence homology with melatonin receptors. The aim of this study was to investigate the effect of GPR50 on inflammation and insulin resistance in 3T3\u2010L1 preadipocytes. GPR50 expression was observed to be significantly increased in the adipose tissue of obese T2DM mice, while GPR50 deficiency increased inflammation in 3T3\u2010L1 cells and induced the phosphorylation of AKT and insulin receptor substrate (IRS) 1. Furthermore, GPR50 knockout in the 3T3\u2010L1 cell line suppressed PPAR\u2010\u03b3 expression. These data suggest that GPR50 can attenuate inflammatory levels and regulate insulin signaling in adipocytes. Furthermore, the effects are mediated through the regulation of the IRS1\/AKT signaling pathway and PPAR\u2010\u03b3 expression.<\/jats:p>","DOI":"10.1002\/2211-5463.13516","type":"journal-article","created":{"date-parts":[[2022,11,5]],"date-time":"2022-11-05T04:15:25Z","timestamp":1667621725000},"page":"89-101","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Orphan receptor\n                    <scp>GPR50<\/scp>\n                    attenuates inflammation and insulin signaling in\n                    <scp>3T3\u2010L1<\/scp>\n                    preadipocytes"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5796-7189","authenticated-orcid":false,"given":"Zhenyu","family":"Yao","sequence":"first","affiliation":[{"name":"Centre for Translational Medicine Research &amp; Development, Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences  Shenzhen 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