TERT and Akt Are Involved in the Par-4-Dependent Apoptosis of Islet β Cells in Type 2 Diabetes

Abstract EN

Islet β cell apoptosis plays an important role in type 2 diabetes.

We previously reported that Par-4-mediated islet β cell apoptosis is induced by high-glucose/fatty acid levels.

In the present study, we show that Par-4, which is induced by high-glucose/fatty acid levels, interacts with and inhibits TERT in the cytoplasm and then translocates to the nucleus.

Par-4 also inhibited Akt phosphorylation, leading to islet β cell apoptosis.

We inhibited Par-4 in islet β cells under high-glucose/fatty acid conditions and knocked out Par-4 in diabetic mice, which led to the up-regulation of TERT and an improvement in the apoptosis rate.

We inhibited Akt phosphorylation in islet β cells and diabetic mice, which led to aggressive apoptosis.

In addition, the biological film interference technique revealed that Par-4 bound to TERT via its NLS and leucine zipper domains.

Our research suggests that Par-4 activation and binding to TERT are key steps required for inducing the apoptosis of islet β cells under high-glucose/fatty acid conditions.

Inhibiting Akt phosphorylation aggravated apoptosis by activating Par-4 and inhibiting TERT, and Par-4 inhibition may be an attractive target for the treatment of islet β cell apoptosis.