GLP-1-Induced AMPK Activation Inhibits PARP-1 and Promotes LXR-Mediated ABCA1 Expression to Protect Pancreatic β-Cells Against Cholesterol-Induced Toxicity Through Cholesterol Efflux

T2DM (Type 2 diabetes) is a complex, chronic disease characterized as insulin resistance and islet β-cell dysfunction. Bariatric surgeries such Roux-en-Y gastric bypass (RYGB) surgery laparoscopic sleeve gastrectomy (LSG) have become part of critical treatment regimen in the obesity T2DM. Moreover, GLP-1 increase following bariatric has been regarded significant event surgery-induced remission In this study, high concentration cholesterol-induced lipotoxicity was observed INS-1 cells, including inhibited cell viability secretion. Enhanced apoptosis cholesterol efflux from cells; meanwhile, ABCA1 protein level decreased by stimulation. Cholesterol-induced toxicity downregulation were attenuated agonist EX-4. induced AMPK phosphorylation during protection against toxicity. Under stimulation, GLP-1-induced activation PARP-1 activity, therefore attenuating cells. directly interacted with LXR, leading to poly(ADP-ribosyl)ation LXRα LXR-mediated expression. STZ-induced model rats, RYGB or EX-4 improved glucose metabolism lipid rats through inhibition activity. conclusion, inhibits protect β function vitro vivo enhancing efflux. expression are involved protective effects.