Berberine modulates insulin signaling transduction in insulin-resistant cells

• Published in: Molecular and cellular endocrinology 2010-04, Vol.317 (1), p.148-153
• Main Authors: Liu, Li-Zhong, Cheung, Stanley C.K., Lan, Lin-Lin, Ho, Stanley K.S., Xu, Hong-Xi, Chan, Juliana C.N., Tong, Peter C.Y.
• Format: Article
• Language: English
• Subjects: Actins; Activation; Animals; Attenuation; Berberine; Berberine - pharmacology; Glucose; Glucose - metabolism; Glucose Transporter Type 4 - metabolism; Insulin; Insulin - metabolism; Insulin Resistance; Insulin signal transduction; L6 muscle cell; Mice; Muscle Cells - drug effects; Muscle Cells - enzymology; Muscle Cells - metabolism; Muscles; Protein Transport - drug effects; Protein-Tyrosine Kinases - metabolism; Rats; Recruitment; Signal Transduction - drug effects; Synergistic effect; Uptakes
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2009.12.027

Berberine has been shown to have insulin-sensitizing effect, but the molecular mechanism underlying remains elusive. In this work, we investigated the effect of berberine on insulin-induced signal transduction and glucose uptake in both insulin-sensitive and insulin-resistant rat skeletal muscle cells. Berberine increased the activity of AMPK and PKCζ and AS160 phosphorylation in normal cells, but had little effect on PKB activation. In insulin-resistant state, berberine exhibited synergistic effect on insulin-induced glucose uptake and GLUT4 translocation. Berberine improved insulin-induced tyrosine-phosphorylation of IRS-1 and the recruitment of p85 to IRS-1. These changes were accompanied by enhancement in insulin-induced PKCζ and PKB activity and actin remodeling. The ameliorated insulin signal transduction was related to the inhibition of mTOR by berberine, which attenuated serine-phosphorylation of IRS-1. These results suggest that berberine may overcome insulin resistance via modulating key molecules in insulin signaling pathway, leading to increased glucose uptake in insulin-resistant cells.