Inhibition of histone acetyltransferase by naringenin and hesperetin suppresses Txnip expression and protects pancreatic β cells in diabetic mice

Schematic diagram of the mechanism. High glucose induces pancreatic β-cell apoptosis by increasing p300/ChREBP mediated Txnip expression. Naringenin and hesperetin inhibit Txnip transcription and protect pancreatic β-cells. In depth, Naringenin and hesperetin activate AMPK to phosphorylate p300, which in turn weaken p300 activity and its interaction with ChREBP. The inactivation of p300 also diminishes its histone acetyltransferase activity and inhibits the occupancy of Pol II in Txnip promoter, impeding high glucose inducedTxnip transcription.Image, graphical abstract