Cornus kousa F.Buerger ex Miguel increases glucose uptake through activation of peroxisome proliferator-activated receptor γ and insulin sensitization

Aim of the study: Corms kousa F.Buerger ex Miguel, an oriental medicinal plant, has been traditionally used for the treatment of hyperglycemia, but its molecular mechanism remains unknown. The goal of this study was to investigate the peroxisome proliferator-activated receptor gamma (PPAR gamma) ligand-binding activity of Corn us kousa and to determine the effects of Corn us kousa on insulin sensitization in 3T3-L1 cells for the treatment of type 2 diabetes. Materials and methods: PPAR gamma luciferase transactivation assay was used to evaluate the PPAR gamma ligand-binding activity of Cornus kousa leaf extract. Western blot analysis, oil Red O staining, and glucose uptake assay were performed to evaluate PPAR gamma agonistic activity and insulin sensitizing effects of Cornus kousa leaf extract (CKE) in 3T3-L1 cells. Results: CKE increased PPAR gamma ligand-binding activity in a dose-dependent manner. In addition, CKE enhanced adipogenesis and the expression of PPAR gamma target proteins, including glucose transporter 4 (GLUT4) and adiponectin, as well as proteins involved in adipogenesis, including PPAR gamma and CCAAT/enhancer binding protein alpha (C/EBP alpha) in 3T3-L1 adipocytes. Furthermore, CKE led to significant induction of glucose uptake and stimulated insulin signaling, but not to activation of AMP-activated protein kinase (AMPK) signaling. The enhanced glucose uptake by CKE were abolished by treatment with bisphenol a diglycidyl ether (BADGE), a PPAR gamma antagonist, or LY294002, an inhibitor of phosphoinositide 3-kinase (PI3K), but not by compound C, an AMPK inhibitor. Conclusion: Consistent with the high PPAR gamma ligand-binding activity, CKE increased glucose uptake through PPAR gamma activation and insulin signaling. These results suggest that CKE could have pharmacological effects for the treatment of hyperglycemia and type 2 diabetes. (C) 2010 Elsevier Ireland Ltd. All rights reserved.