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Berberine reduces endoplasmic reticulum stress and improves insulin signal transduction in Hep G2 cells

Zeng-si Wang,F. Lu,Li-jun Xu,Hui Dong

Published 2010 in Acta Pharmacologica Sinica

ABSTRACT

AbstractAim:Endoplasmic reticulum (ER) stress plays an important role in the pathogenesis of insulin resistance and pancreatic β-cell dysfunction. The aim of this study is to investigate whether the insulin-sensitizing action of berberine is related to reducing ER stress.Methods:ER stress in cultured Hep G2 cells was induced with tunicamycin. Cells were pretreated with berberine in combination with or without insulin. The concentration of glucose was measured by glucose oxidase method. The molecular markers of ER stress, including ORP150, PERK, and eIF2α were analyzed by Western blot or real time PCR. The activity of JNK was also evaluated. Moreover, the insulin signaling proteins such as IRS-1 and AKT were determined by Western blot.Results:The production of glucose stimulated with insulin was reduced. The expressions of ORP150 was decreased both in gene and protein levels when cells were pretreated with berberine, while the activation of JNK was blocked. The levels of phosphorylation both on PERK and eIF2α were inhibited in cells pretreated with berberine. The level of IRS-1 ser307 phosphorylation was decreased, whereas IRS-1 tyr phosphorylation was increased notablely. AKT ser473 phosphorylation was also enhanced significantly in the presence of berberine.Conclusion:The antidiabetic effect of berberine in Hep G2 cells maybe related to attenuation of ER stress and improvement of insulin signal transduction.

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