A hydroxychalcone derived from cinnamon functions as a mimetic for insulinin 3T3-L1 adipocytes

Objectives: These studies investigated the ability of a hydroxychalcone fro m cinnamon to function as an insulin mimetic in 3T3-L1 adipocytes. Methods: Comparative experiments were performed with the cinnamon methylhyd roxychalcone polymer and insulin with regard to glucose uptake, glycogen sy nthesis, phosphatidylinositol-3-kinase dependency, glycogen synthase activa tion and glycogen synthase kinase-3 beta activity. The phosphorylation stat e of the insulin receptor was also investigated. Results: MHCP treatment stimulated glucose uptake and glycogen synthesis to a similar level as insulin. Glycogen synthesis was inhibited by both wortm annin and LY294002, inhibitors directed against the PI-3-kinase. In additio n, MHCP treatment activated glycogen synthase and inhibited glycogen syntha se kinase-3 beta activities, known effects of insulin treatment. Analysis o f the insulin receptor demonstrated that the receptor was phosphorylated up on exposure to the MHCP. This supports that the insulin cascade was trigger ed by MHCP. Along with comparing MHCP to insulin, experiments were done wit h MHCP and insulin combined. The responses observed using the dual treatmen t were greater than additive, indicating synergism between the two compound s. Conclusion: Together, these results demonstrate that the MHCP is an effecti ve mimetic of insulin. MHCP may be useful in the treatment of insulin resis tance and in the study of the pathways leading to glucose utilization in ce lls.