Tranilast protects pancreatic β-cells from palmitic acid-induced lipotoxicity via FoxO-1 inhibition.

ABSTRACT: Tranilast, an anti-allergic drug used in the treatment of bronchial asthma, was identified as an inhibitor of the transcription factor Forkhead box O-1 (FoxO-1) by high throughput chemical library screening in the present study. Based on FoxO-1's role in apoptotic cell death and differentiation, we examined the effect of tranilast on palmitic acid (PA)-induced cell damage in INS-1 cells. Tranilast substantially inhibited lipoapoptosis and restored glucose-stimulated insulin secretion under high PA exposure. Moreover, PA-mediated downregulation of PDX-1, MafA, and insulin expression was attenuated by tranilast. PA-induced oxidative and ER stress were also reduced in the presence of tranilast. These protective effects were accompanied by increased phosphorylation and decreased nuclear transl

SUBMITTER: Choi HE 

PROVIDER: S-EPMC9810694 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature