Berberine modulates insulin signaling transduction in insulin-resistant cells.
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 PKCzeta 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 PKCzeta 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.
Liu
Li-Zhong
LZ
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, N.T., Hong Kong, China.
Cheung
Stanley C K
SC
Lan
Lin-Lin
LL
Ho
Stanley K S
SK
Xu
Hong-Xi
HX
Chan
Juliana C N
JC
Tong
Peter C Y
PC
D000199:Actins; D000818:Animals; D001599:Berberine / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D051379:Mice; D032342:Muscle Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*
D000199:Actins; D051275:Glucose Transporter Type 4; D007328:Insulin; D001599:Berberine; C410467:insulin receptor tyrosine kinase; D011505:Protein-Tyrosine Kinases; D005947:Glucose