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 T2 DM is often associated with insulin resistance and impaired glucose uptake in peripheral tissues. In this study, we examined whether BBR attenuated glucose uptake dysfunction through the cholinergic anti-inflammatory pathway in Hep G2 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 Hep G2 cells were incubated with insulin(10-6 mol/L) for 36 h. Meanwhile, the expression of alpha7 nicotinic acetylcholine receptor(α7n ACh R) protein was reduced without the change of acetylcholinesterase(ACh E) activity. The level of interleukin-6(IL-6) in the culture supernatant, the ratio of phosphorylated I-kappa-B kinase-β(IKKβ) Ser181/IKKβ and the expression of nuclear factor-kappa B(NF-κB) p65 protein were also increased. However, the treatment with BBR enhanced the glucose uptake, increased the expression of α7n ACh R protein and inhibited ACh E activity. These changes were also accompanied with the decrease of the ratio of p IKKβ Ser181/IKKβ, NF-κB p65 expression and IL-6 level. Taken together, these results suggest that BBR could enhance glucose uptake, and relieve insulin resistance and inflammation in Hep G2 cells. The mechanism may be related to the cholinergic anti-inflammatory pathway and the inhibition of ACh E activity.