Grape seed-derived procyanidins decrease dipeptidyl-peptidase 4 activity and expression.
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.
Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Tarragona, Spain.
Noemi
N
González-Abuín
Neus
N
Martínez-Micaelo
Mayte
M
Blay
Gerard
G
Pujadas
Santiago
S
Garcia-Vallvé
Montserrat
M
Pinent
Anna
A
Ardévol
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D018938:Caco-2 Cells; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics* / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D056604:Grape Seed Extract / Q000494:pharmacology*; D006801:Humans; D044945:Proanthocyanidins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011924:Rats, Zucker; D027843:Vitis / Q000737:chemistry*
D001786:Blood Glucose; D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D044945:Proanthocyanidins; D018819:Dipeptidyl Peptidase 4