文献类型：期刊文献

英文题名：2′,4′-Dihydroxy-6′-methoxy-3′,5′-dimethylchalcone Protects the Impaired Insulin Secretion Induced by Glucotoxicity in Pancreatic β-Cells

作者：Hu, Ying-Chun[1,2];Hao, Dong-Ming[3];Zhou, Lu-Xian[2];Zhang, Zhe[2];Huang, Nan[2];Hoptroff, Michael[2];Lu, Yan-Hua[1]

机构：[1]E China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Unilever R&D Shanghai, Shanghai 200335, Peoples R China;[3]Tianjin Union Med Ctr, Dept Anus & Intestine Surg, Tianjin 300121, Peoples R China

年份：2014

卷号：62

期号：7

起止页码：1602

外文期刊名：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY

收录：;EI(收录号：20151600745640);WOS:【SCI-EXPANDED(收录号:WOS:000331779400022)】；

基金：This work was supported by "the Fundamental Research Funds for the Central Universities", and partially supported by Shanghai Leading Academic Discipline Project (B505), the National Special Fund for State Key Laboratory of Bioreactor Engineering (2060204).

语种：英文

外文关键词：2 ',4 '-Dihydroxy-6 '-methoxy-3 ',5 '-dimethylchalcone; glucotoxicity; insulin secretion; PDX-1; oxidative stress

摘要：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 c-ytotoxicity level for 48 h, MN-SF beta-cells experienced a significant viability loss and impaired insulin secretion function, whereas cotreating with DMC could protect beta-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.