ABSTRACT
2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC), one of the flavonoids isolated and purified from the dried flower buds of Cleistocalyx operculatus, was explored for its function in glucose uptake/glycogen synthesis in insulin-sensitive tissue cells and its effect and mechanism on 3T3-L1 preadipocyte differentiation. DMC (10 µM) treatment remarkably promoted glucose uptake in differentiated 3T3-L1 adipocytes (P < 0.05 vs control group), whereas the glucose uptake in L6 myoblasts and glycogen synthesis in HepG2 hepatocytes were not affected by the treatment. DMC had paradoxical effects on lipid accumulation in 3T3-L1 cells compared with differentiation control. High concentrations of DMC (10 and 20 µM) markedly diminished lipid accumulation; however, a low concentration of DMC (2.5 µM) enhanced lipid storage in 3T3-L1 cells (P < 0.01 vs differentiation control group), and 5 µM DMC did not impose a significant effect. It was demonstrated that the effect of DMC in lipid accumulation was controlled by the expression of PPAR-γ.
Subject(s)
Adipocytes/drug effects , Cell Differentiation/drug effects , Chalcones/pharmacology , Glucose/metabolism , Myrtaceae/chemistry , Plant Extracts/pharmacology , 3T3-L1 Cells , Adipocytes/cytology , Adipocytes/metabolism , Animals , Biological Transport/drug effects , Chalcones/adverse effects , Glucose Transporter Type 4/genetics , Glucose Transporter Type 4/metabolism , Hep G2 Cells , Humans , Mice , PPAR gamma/genetics , PPAR gamma/metabolism , Up-RegulationABSTRACT
2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC), which is isolated and purified from the dried flower buds of Cleistocalyx operculatus (Roxb.) Merr. et Perry (Myrtaceae), was investigated for its insulinotropic benefits against glucotoxicity using in vitro methods. When exposed to high glucose at the cytotoxicity level for 48 h, RIN-5F ß-cells experienced a significant viability loss and impaired insulin secretion function, whereas cotreating with DMC could protect ß-cells against glucotoxicity-induced decrease in glucose-stimulated insulin secretion in a dose-dependent manner without affecting basal insulin secretion. It was demonstrated that DMC increased insulin secretion against glucotoxicity by simulating the effect of GLP-1 and enhancing the expression of GLP-1R, followed by activating the signal pathway of PDX-1, PRE-INS, and GLUT2-GCK. Another mechanism was that DMC avoided the pancreatic islet dysfunction resulting from cellular damage by suppressing the production of nitric oxide (NO) by iNOS, and the expression of MCP-1. The results indicated the potential application of DMC in the intervention against glucotoxicity-induced hyperglycemia.
