Par-4NF-κB Mediates the Apoptosis of Islet β Cells Induced by Glucolipotoxicity

Abstract EN

Apoptosis of islet β cells is a primary pathogenic feature of type 2 diabetes, and ER stress and mitochondrial dysfunction play important roles in this process.

Previous research has shown that prostate apoptosis response-4 (Par-4)/NF-κB induces cancer cell apoptosis through endoplasmic reticulum (ER) stress and mitochondrial dysfunction.

However, the mechanism by which Par-4/NF-κB induces islet β cell apoptosis remains unknown.

We used a high glucose/palmitate intervention to mimic type 2 diabetes in vitro.

We demonstrated that the high glucose/palmitate intervention induced the expression and secretion of Par-4.

It also causes increased expression and activation of NF-κB, which induced NIT-1 cell apoptosis and dysfunction.

Overexpression of Par-4 potentiates these effects, whereas downregulation of Par-4 attenuates them.

Inhibition of NF-κB inhibited the Par-4-induced apoptosis.

Furthermore, these effects occurred through the ER stress cell membrane and mitochondrial pathway of apoptosis.

Our findings reveal a novel role for Par-4/NF-κB in islet β cell apoptosis and type 2 diabetes.