Quercetin promotes long noncoding RNA lncSHGL expression via estrogen receptor α to suppress type 2 diabetes mellitus in mice

Abstract Background Type 2 diabetes mellitus (T2DM) is the most common type of metabolic disorder involving multiple organ systems. Grape has been reported to improve the symptoms of T2DM, the precise mechanism of its action is unclear. Our study was aimed to determine the effect and mechanism of grape pomace extract in T2DM mice induced by high fat diet (HFD). Materials and methods Ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry were used to identify the main active compounds in grape pomace extract to improve T2DM. C57BLK/6J mice induced by HFD supplemented with or without quercetin were used to show the effects of quercetin improving T2DM. By online database research, bioinformatics analysis and molecular biology experiments, Estrogen receptor alpha (ERα)-lncSHGL (lncRNA suppressor of hepatic gluconeogenesis and lipogenesis) pathway was identify as the target for quercetin. Results Quercetin was identified as one of the most active compounds in grape pomace extract to improve T2DM. Quercetin could inhibit HFD-induced T2DM in mice by activing ERα. LncSHGL was identified as the downstream of ERα and inhibited HFD-induced T2DM. Conclusions Quercetin could be beneficial for T2DM by promoting lncSHGL transcription and activating the lncSHGL pathway, and may be used as a drug component to treat T2DM.