Grape Seed-Derived Procyanidins Decrease Dipeptidyl-peptidase 4 Activity and Expression

• Published in: Journal of agricultural and food chemistry 2012-09, Vol.60 (36), p.9055-9061
• Main Authors: González-Abuín, Noemi, Martínez-Micaelo, Neus, Blay, Mayte, Pujadas, Gerard, Garcia-Vallvé, Santiago, Pinent, Montserrat, Ardévol, Anna
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; blood glucose; Blood Glucose - metabolism; Caco-2 Cells; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - enzymology; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - metabolism; Dipeptidyl Peptidase 4 - genetics; Dipeptidyl Peptidase 4 - metabolism; Down-Regulation - drug effects; Female; flavonoids; Food industries; Fruit and vegetable industries; Fundamental and applied biological sciences. Psychology; gene expression; Gene Expression - drug effects; gene expression regulation; glucose; Grape Seed Extract - pharmacology; grapes; homeostasis; Humans; noninsulin-dependent diabetes mellitus; Proanthocyanidins - pharmacology; procyanidins; Rats; Rats, Wistar; Rats, Zucker; Vitis - chemistry
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf3010349

Dipeptidyl-peptidase 4 (DPP4) inhibitors are among the newest treatments against type 2 diabetes. Since some flavonoids modulate DPP4 activity, we evaluated whether grape seed-derived procyanidins (GSPEs), which are antihyperglycemic, modulate DPP4 activity and/or expression. In vitro inhibition assays showed that GSPEs inhibit pure DPP4. Chronic GSPE treatments in intestinal human cells (Caco-2) showed a decrease of DPP4 activity and gene expression. GSPE was also assayed in vivo. Intestinal but not plasmatic DPP4 activity and gene expression were decreased by GSPE in healthy and diet-induced obese animals. Healthy rats also showed glycemia improvement after oral glucose consumption but not after an intraperitoneal glucose challenge. In genetically obese rats, only DPP4 gene expression was down-regulated. Thus, procyanidin inhibition of intestinal DPP4 activity, either directly and/or via gene expression down-regulation, could be responsible for some of their effects in glucose homeostasis.