Low glucose enhances Na+/glucose transport in bovine brain artery endothelial cells

Brain arteries are structurally characterized by the tight junctions of the endothelium and by no vasa vasorum that feed arteries themselves. This raises the question of how brain arteries are provided with glucose. A possible explanation is that glucose uptake into arteries may be mediated by both GLUT1, a facilitative glucose transporter, and a Na+/glucose cotransporter (SGLT)-like glucose transporter. The functional role for the SGLT-like glucose transporter, however, is unknown. In the present study we investigated SGLT-like glucose transporter-operated glucose uptake into brain arterial endothelial cells by recording glucose-evoked Na+ currents and monitoring uptake of [3H]-2-deoxy-D-glucose ([3H]-2-DOG).

Endothelial cells were cultured from bovine cerebral cortical arteries. Whole-cell patches were made to cells, and glucose-evoked currents were recorded. Cells were incubated with [3H]-2-DOG, and the uptake was determined by a liquid scintillation counter.

Glucose and alpha-methyl-D-glucoside (alphaMeDG), a specific compound for the SGLTs, evoked Na+ currents in a whole-cell voltage-clamp configuration, and the currents were enhanced in cells with over 30 minutes' preincubation in glucose-free media. Glucose-induced currents were inhibited by alphaMeDG, by the selective SGLT inhibitor phlorizin, by dinitrophenol (DNP), an inhibitor of energy metabolism, or by deletion of Na+ from extracellular solution, which indicates that glucose uptake into endothelial cells was mediated by a Na+- and energy-dependent glucose transporter. Notably, the currents were desensitized, reduced in a glucose concentration-dependent manner, and markedly inhibited by either a second application of glucose or the addition of glucose to the patch electrode filling solution; they were potentiated, however, by treatment with cytochalasin B, a GLUT1 to GLUT5 inhibitor. Consistent with the results of patch-clamp recordings, uptake of [3H]-2-DOG into endothelial cells was enhanced by glucose-free insult, and the enhancement was mediated by an SGLT-like glucose transporter.

The results presented demonstrate that an SGLT-like glucose transporter takes part in glucose uptake into brain artery endothelial cells and that the uptake is regulated by intracellular glucose concentrations; glucose-free insult and the ensuing low cytosolic glucose enhance activity of the SGLT-like glucose transporter. The SGLT-like glucose transporter in the brain arterial endothelium thus may be important in the maintenance of an adequate glucose concentration in the arterial wall under conditions of stress, such as hypoglycemia.