Li_2016_J.Huazhong.Univ.Sci.Technolog.Med.Sci_36_64

Berberine (BBR) is an isoquinoline alkaloid extracted from Rhizoma coptidis and has been used for treating type 2 diabetes mellitus (T2DM) in China. The development of T2DM is often abetasociated with insulin resistance and impaired glucose uptake in peripheral tibetasues. In this study, we examined whether BBR attenuated glucose uptake dysfunction through the cholinergic anti-inflammatory pathway in HepG2 cells. Cellular glucose uptake, quantified by the 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)-amino]-2-deoxy-D-glucose (2-NBDG), was inhibited by 21% after HepG2 cells were incubated with insulin (10(-6) mol/L) for 36 h. Meanwhile, the exprebetasion of alpha7 nicotinic acetylcholine receptor (alpha7nAChR) protein was reduced without the change of acetylcholinesterase (AChE) activity. The level of interleukin-6 (IL-6) in the culture supernatant, the ratio of phosphorylated I-kappa-B kinase-beta (IKkappabeta) Ser181/IKKbeta and the expression of nuclear factor-kappa B (NF-kappaB) p65 protein were also increased. However, the treatment with BBR enhanced the glucose uptake, increased the expression of alpha7nAChR protein and inhibited AChE activity. These changes were also accompanied with the decrease of the ratio of pIKKbeta Ser181/IKKbeta, NF-kappaB p65 expression and IL-6 level. Taken together, these results suggest that BBR could enhance glucose uptake, and relieve insulin resistance and inflammation in HepG2 cells. The mechanism may be related to the cholinergic anti-inflammatory pathway and the inhibition of AChE activity.