Metformin-induced regulation of the intestinal D-glucose transporters.

Abstract : Metformin is an orally administered drug that lowers blood glucose and improves insulin sensitivity in patients with non insulin-dependent diabetes. Although the antihyperglycemic effect of metformin has been extensively studied, its cellular mechanism(s) of action (including the effect on enterocyte) remains to be defined. This study was designed to examine the effect of metformin on glucose transporters in enterocyte. Na(+)-dependent glucose transporter-1 (SGLT-1) activity was followed as glucose-induced short-circuit current (Isc) in Ussing chambers. The effect of metformin (10 micromol/L, 3 min) on transmural glucose transport was studied in isolated rat jejunal loops. Its impact on abundance of transporters SGLT-1 and GLUT2 in jejunal brush border membranes (BBM) and its effect on the phosphorylation of AMP-activated protein kinase (AMPK) alpha2 subunit was studied by western blot. Acute effect of metformin was also measured in vivo by oral glucose tolerance test (OGTT). Metformin markedly inhibited glucose-induced Isc (approximately 77%) after mucosal addition. In addition, metformin reduced the glucose-induced abundance of SGLT-1 in BBM and increased those of GLUT2, concomitantly increasing the phosphorylation of intracellular AMPKalpha2. This effect of metformin was also observed using non-metabolizable sugar alpha3-O-methyl glucose. Transmural glucose transport measured in vitro was increased by 22% under metformin. Finally, oral metformin markedly increased glucose tolerance in OGTT. In conclusion, metformin slightly increases intestinal glucose absorption by inducing a re-distribution of glucose transporters in BBM through AMPK control in enterocyte. In addition to its action to other splanchnic tissues, this could constitute a peripheral signal contributing to the beneficial effect of metformin on glucose tolerance.
Type de document :
Article dans une revue
Journal of Physiology and Pharmacology, Krakow Polish Physiological Society, 2010, 61 (3), pp.301-7
Liste complète des métadonnées

http://www.hal.inserm.fr/inserm-00501629
Contributeur : <>
Soumis le : lundi 12 juillet 2010 - 14:29:55
Dernière modification le : mardi 11 octobre 2016 - 13:56:37
Document(s) archivé(s) le : jeudi 30 mars 2017 - 00:44:58

Fichier

 Accès restreint
Fichier visible le : jamais

Connectez-vous pour demander l'accès au fichier

Identifiants

  • HAL Id : inserm-00501629, version 1
  • PUBMED : 20610860

Collections

Citation

Yassine Sakar, Bouchra Meddah, Moulay El Abbes Faouzi, Yahia Cherrah, André Bado, et al.. Metformin-induced regulation of the intestinal D-glucose transporters.. Journal of Physiology and Pharmacology, Krakow Polish Physiological Society, 2010, 61 (3), pp.301-7. 〈inserm-00501629〉

Partager

Métriques

Consultations de la notice

120