Regulation of Na+-coupled glucose carrier SGLT1 by AMP-activated protein kinase.

AMP-activated protein kinase (AMPK), a serine/threonine kinase activated upon energy depletion, stimulates energy production and limits energy utilization. It has previously been shown to enhance cellular glucose uptake through the GLUT family of facilitative glucose transporters. The present study explored the possibility that AMPK may regulate Na+-coupled glucose transport through SGLT1 (SLC5A1). To this end, SGLT1 was expressed in Xenopus oocytes with and without AMPK and electrogenic glucose transport determined by dual electrode voltage clamping experiments. In SGLT1-expressing oocytes but not in oocytes injected with water or expressing constitutively active (gammaR70Q)AMPK (alpha1beta1gamma1(R70Q)) alone, the addition of glucose to the extracellular bath generated a current (I(g)), which was half maximal (K(M)) at approximately 650 microM glucose concentration. Coexpression of (gammaR70Q)AMPK did not affect K(M) but significantly enhanced the maximal current (approximately 1.7 fold). Coexpression of wild type AMPK or the kinase dead (alphaK45R)AMPK mutant (alpha1(K45R)beta1gamma1) did not appreciably affect I(g). According to confocal microscopy and Western Blotting, AICAR (1 mM), phenformin (1 mM) and A-769662 (10 microM) enhanced the SGLT1 protein abundance in the cell membrane of Caco2 cells suggesting that AMPK activity may increase membrane translocation of SGLT1. These observations support a role for AMPK in the regulation of Na+-coupled glucose transport.