FXR?mediated epigenetic regulation of GLP?1R expression contributes to enhanced incretin effect in diabetes after RYGB

In this study, we investigated how Roux-en-Y gastric bypass (RYGB) enhances glucagon-like peptide 1 (GLP-1) response in GK rats and explored the potential link between RYGB-stimulated BAs/FXR signalling GLP-1R-linked ?-cells, a key pathway that regulates glucose-stimulated insulin secretion (GSIS). Here show RYGB restores GLP-1R expression rat islets. This involves increased total BAs as well chenodeoxycholic acid (CDCA), leading to FXR activation, increasing binding promoter of Glp-1r enhancing occupancy histone acetyltransferase steroid receptor coactivator-1 (SRC1), thus H3 acetylation at promoter. These coordinated events bring about expression, resulting greater GLP-1 ?-cells. Moreover, ablation suppressed stimulatory effects GLP-1. Thus, study unravels crucial role BAs/FXR/SRC1 axis-controlled which results enhanced incretin effect normalized blood glucose after RYGB.