Metformin-induced regulation of the intestinal D-glucose transporters

• Autorzy: Sakar Y. , Meddah B. , Faouzi M.A. , Cherrah Y. , Bado A. , Ducroc R.
• Języki publikacji: EN

Abstrakty

EN

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 µmol/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) 2 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 (~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 AMPK2. This effect of metformin was also observed using non-metabolizable sugar 3-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.

Słowa kluczowe

EN

metformin; D-glucose transporter; blood glucose; patient; insulin-dependent diabetes; diabetes; antihyperglycemic effect; cellular mechanism; enterocyte; glucose tolerance; AMP-activated protein kinase; sodium-dependent glucose transporter-1

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology
• Rocznik: 2010
• Tom: 61
• Numer: 3
• Opis fizyczny: p.301-307,fig.,ref.

Twórcy

autor

Sakar Y.

• Universite Denis Diderot, UMR S 773, 16 rue Henri Huchard, 75890 Paris cedex 18, France

autor

Meddah B.

autor

Faouzi M.A.

autor

Cherrah Y.

autor

Bado A.

autor

Ducroc R.

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