Synergistic effect of curcumin and insulin on muscle cell glucose metabolism

Curcumin is a major phenolic compound of Curcuma longa, which has long been used in traditional Indian medicine. Recently, curcumin has been reported to have antihyperglycemic activity in animal models. However, the molecular basis of this action has not been adequately described. In the present study, curcumin was observed to contain a high level of polyphenols and strong antioxidant activity. Then, the antihyperglycemic effect of curcumin was examined for various signaling pathways using C(2)C(12) mouse myoblast cells. From this, curcumin treatment strongly induced glucose uptake and the phosphorylation of AMPK (AMP-activated protein kinase)/ACC (acetyl-CoA carboxylase), but not PI3-kinase (phosphoinositide 3-kinase)/Akt. Interestingly, the co-treatment of insulin and curcumin produced a mutual synergistic activation of both AMPK/ACC and PI3-kinase/Akt pathways. On the other hand, the synergism could not be observed from the co-treatment of insulin and EGCG. It suggests that the two signaling pathways can crosstalk each other in a case-sensitive manner upon the treatment of antioxidant polyphenols. Further, these results were consistent with the findings of GLUT4 translocation to the cell surface. Our findings indicate that curcumin can promote AMPK activation and glucose uptake with increased insulin sensitivity in muscle cells as a potential anti-diabetic therapeutic agent.