Cornus kousa F.Buerger ex Miquel increases glucose uptake through activation of peroxisome proliferator-activated receptor γ and insulin sensitization.
OBJECTIVE
Cornus kousa F.Buerger ex Miquel, 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 γ (PPARγ) ligand-binding activity of Cornus kousa and to determine the effects of Cornus kousa on insulin sensitization in 3T3-L1 cells for the treatment of type 2 diabetes.


METHODS
PPARγ luciferase transactivation assay was used to evaluate the PPARγ ligand-binding activity of Cornus kousa leaf extract. Western blot analysis, oil Red O staining, and glucose uptake assay were performed to evaluate PPARγ agonistic activity and insulin sensitizing effects of Cornus kousa leaf extract (CKE) in 3T3-L1 cells.


RESULTS
CKE increased PPARγ ligand-binding activity in a dose-dependent manner. In addition, CKE enhanced adipogenesis and the expression of PPARγ target proteins, including glucose transporter 4 (GLUT4) and adiponectin, as well as proteins involved in adipogenesis, including PPARγ and CCAAT/enhancer binding protein α (C/EBPα) 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 PPARγ antagonist, or LY294002, an inhibitor of phosphoinositide 3-kinase (PI3K), but not by compound C, an AMPK inhibitor.


CONCLUSIONS
Consistent with the high PPARγ ligand-binding activity, CKE increased glucose uptake through PPARγ activation and insulin signaling. These results suggest that CKE could have pharmacological effects for the treatment of hyperglycemia and type 2 diabetes.
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.
Daeyoung
D
Kim
Kwang-Kyun
KK
Park
Sang Kook
SK
Lee
Seung-Eun
SE
Lee
Jae-Kwan
JK
Hwang
D041721:3T3-L1 Cells; D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D029768:Cornus; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism; D020834:Ethnopharmacology; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D008024:Ligands; D055670:Medicine, Korean Traditional; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism*; D008517:Phytotherapy; D028321:Plant Preparations / Q000008:administration & dosage / Q000494:pharmacology*; D010946:Plants, Medicinal; D056910:Republic of Korea; D015398:Signal Transduction / Q000187:drug effects
D007328:Insulin; D008024:Ligands; D047495:PPAR gamma; D028321:Plant Preparations; D005947:Glucose