Effects of Genistein on Inflammasome Induced Pancreatic β‐Cell Apoptosis by Dexamethasone

Steroid‐induced diabetes is a well‐known side effect of prolonged glucocorticoid (GC) treatment. Endoplasmic reticulum (ER) stress has been identified as one of the mechanisms underlying GC‐induced pancreatic β‐cell apoptosis. Recent studies suggest a connection between ER stress and the NLRP3 inflammasome, which promotes cell apoptosis. Genistein, a phytoestrogen, has demonstrated protective effects against pancreatic β‐cell apoptosis induced by toxic agents. This study aims to investigate whether genistein protects against dexamethasone‐induced pancreatic β‐cell apoptosis by reducing ER stress and NLRP3 inflammasome activation. This study demonstrates that dexamethasone induces pancreatic β‐cell apoptosis by increasing cPARP protein expression. Dexamethasone upregulates SERCA, IRE1‐α, and sXBP expressions, while increasing pJNK and Bax and decreasing Bcl‐2 protein expressions. Furthermore, dexamethasone upregulates TXNIP, a link protein between ER stress and the NLRP3 inflammasome, and increases NLRP3 and ASC, components of the NLRP3 inflammasome, leading to increase IL‐1β expressions. Co‐treatment of dexamethasone with genistein decreases cPARP expression, reduces SERCA, IRE1‐α, sXBP, pJNK, and Bax, and induces Bcl‐2 expressions. Co‐treatment significantly decreases TXNIP, NLRP3, ASC, and IL‐1β expressions. Similar results were observed in pancreatic islets for cPARP, NLRP3, and IL‐1β. This study demonstrates that genistein protects against dexamethasone‐induced pancreatic β‐cell apoptosis by decreasing ER stress and the NLRP3 inflammasome.