2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone protects the impaired insulin secretion induced by glucotoxicity in pancreatic β-cells.
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 β-cells experienced a significant viability loss and impaired insulin secretion function, whereas cotreating with DMC could protect β-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.
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology , 130 Meilong Road, Shanghai 200237, P. R. China.
Ying-Chun
YC
Hu
Dong-Ming
DM
Hao
Lu-Xian
LX
Zhou
Zhe
Z
Zhang
Nan
N
Huang
Michael
M
Hoptroff
Yan-Hua
YH
Lu
D000818:Animals; D045744:Cell Line, Tumor; D047188:Chalcones / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000378:metabolism / Q000633:toxicity*; D051273:Glucose Transporter Type 2 / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D027822:Myrtaceae / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
C501649:2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone; D047188:Chalcones; D051273:Glucose Transporter Type 2; D018398:Homeodomain Proteins; D007328:Insulin; D010936:Plant Extracts; D020011:Protective Agents; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D005947:Glucose