Berberine relieves insulin resistance via the cholinergic anti-inflammatory pathway in HepG2 cells

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 a beta sociated with insulin resistance and impaired glucose uptake in peripheral ti beta sues. 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 expre beta sion of alpha7 nicotinic acetylcholine receptor (alpha 7nAChR) 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 (IK kappa I-2) Ser181/IKK beta and the expression of nuclear factor-kappa B (NF-kappa B) p65 protein were also increased. However, the treatment with BBR enhanced the glucose uptake, increased the expression of alpha 7nAChR protein and inhibited AChE activity. These changes were also accompanied with the decrease of the ratio of pIKK beta Ser181/IKK beta, NF-kappa B 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.