Baicalein protects rat insulinoma INS-1 cells from palmitate-induced lipotoxicity by inducing HO-1.

ABSTRACT:

Objective

?-Cell dysfunction plays a central role in the pathogenesis of type 2 diabetes (T2D), and the identification of novel approaches to improve ?-cell function is essential to treat this disease. Baicalein, a flavonoid originally isolated from the root of Scutellaria Baicalensis, has been shown to have beneficial effects on ?-cell function. Here, the authors investigated the molecular mechanism responsible for the protective effects of baicalein against palmitate (PA)-induced impaired ?-cell function, and placed focus on the role of heme oxygenase (HO)-1.

Methods

Rat pancreatic ?-cell line INS-1 cells or mouse pancreatic islets were cultured with PA (500 ?M) to induce lipotoxicity in the presence or absence of baicalein (50 ?M), and the expressions of the ER stress markers, ATF-3, CHOP and GRP78 were detected by Western blotting and/or qPCR. The involvement of HO-1 was evaluated by HO-1 siRNA transfection and using the HO-1 inhibitor ZnPP.

Results

Baicalein reduced PA-induced ER stress and inflammation and enhanced insulin secretion, and these effects were associated with the induction of HO-1. Furthermore, these protective effects were attenuated by ZnPP and by HO-1 siRNA. Pretreatment of PD98059 (an ERK inhibitor) significantly inhibited the protective effects of baicalein and blocked HO-1 induction. On the other hand, CO production by RuCO (a CO donor) ameliorated PA-induced ER stress, suggesting that CO production followed by HO-1 induction may contribute to the protective effects of baicalein against PA-induced ?-cell dysfunction.

Conclusion

Baicalein protects pancreatic ?-cells from PA-induced ER stress and inflammation via an ERK-HO-1 dependent pathway. The authors suggest HO-1 induction in pancreatic ?-cells appears to be a promising therapeutic strategy for T2D.

SUBMITTER: Kwak HJ 

PROVIDER: S-EPMC5405981 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature