Angiotensin II promotes the expression of TXNIP through angiotensin II type 1 receptor in islet β cells / 生理学报

ABSTRACT

This study investigated the effect of angiotensin II (Ang II) on apoptosis and thioredoxin-interacting protein (TXNIP) expression in INS-1 islet cells and the underlying mechanism. INS-1 cells cultured in vitro were treated with different concentration of Ang II for different time, and the viability was measured using cell counting kit-8 (CCK-8). After treatment with 1 × 10 mol/L Ang II for 24 h, flow cytometry and Western blot were used to measure the cell apoptosis, and Western blot was used to analyze the protein expression of TXNIP, carbohydrate response element-binding protein (ChREBP) and angiotensin II type 1 receptor (AT1R). Real-time PCR was used to detect TXNIP and ChREBP mRNA expression. IF/ICC was used to observe the TXNIP, ChREBP and AT1R expression. The results showed that Ang II reduced cell viability and induced the expression of TXNIP in a dose- and time-dependent manner (P < 0.05, n = 6) compared with the control group. Ang II induced apoptosis and up-regulated the expression of ChREBP and AT1R (P < 0.05, n = 6). AT1R inhibitor, telmisartan (TM), blocked Ang II-induced TXNIP and ChREBP overexpression (P < 0.05, n = 6) and inhibited Ang II-induced apoptosis. Taken together, Ang II increased ChREBP activation through AT1R, which subsequently increased TXNIP expression and promoted cell apoptosis. These findings suggest a therapeutic potential of targeting TXNIP in preventing Ang II-induced INS-1 cell apoptosis in diabetes.