Interaction of flavonoids and intestinal facilitated glucose transporters.
The intestinal facilitated glucose transporter, GLUT2, is a high-turnover transport system and is important to handle the large transepithelial substance flux. Since intestinal GLUT2 is normally located at the basolateral side, glucose uptake in the presence of flavonoids was measured using basolateral membrane vesicles (BLMV) isolated from the rat jejunum to investigate the interaction between flavonoids and intestinal facilitated glucose transporters. In addition, basolateral uptake of flavonoids was studied in Caco-2 cells. As a result, in the BLMV study most flavonoids (glycosides or aglycones) at 0.1 mM inhibited glucose uptake in BLMV; epicatechin gallate (ECG) showed the highest inhibitory activity (about 33%), followed by quercetin 3-O-glucoside (Q3G), fisetin and gossypin (about 25-28% inhibition). The dose-response study showed that the IC50 values for ECG and Q3G on glucose uptake in BLMV were 294+/-89 microM and 357+/-52 microM, respectively. Kinetic analyses showed that ECG and Q3G competitively inhibited glucose uptake in BLMV with inhibition constants (Ki) of 332+/-42 microM and 404+/-45 microM, respectively. In Caco-2 cells, basolateral uptake of Q3G was significantly inhibited by phloretin, a GLUT2 inhibitor (0.40+/-0.05 vs. 0.24+/-0.03 nmole/mg protein without aand with phloretin, respectively). On the other hand, phloretin did not show inhibitory activity on basolateral uptake of ECG in Caco-2 cells (1.26+/-0.05 vs. 1.22+/-0.07 nmole/mg protein without and with phloretin, respectively). The data showed that the intestinal facilitated glucose transporter recognizes a variety of flavonoids with or without conjugation. In addition, GLUT2 can be responsible for the transport of Q3G across the intestinal basolateral membrane.
Chen
Chia-Hao
CH
School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan.
Hsu
Hao-Jui
HJ
Huang
Yun-Ju
YJ
Lin
Chun-Jung
CJ
D000818:Animals; D018938:Caco-2 Cells; D004357:Drug Synergism; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology*; D005947:Glucose / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism*; D006801:Humans; D020128:Inhibitory Concentration 50; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008517:Phytotherapy; D010946:Plants, Medicinal; D011794:Quercetin / Q000031:analogs & derivatives; D051381:Rats; D017208:Rats, Wistar
D005419:Flavonoids; D051246:Glucose Transport Proteins, Facilitative; C012526:quercitrin; D011794:Quercetin; D005947:Glucose