Glucose uptake by C6 glioma cells is mediated by G(q alpha)

The role of G proteins in glucose uptake was investigated using C6 glioma cells. Carbachol (an agonist acting via G protein coupled receptors) and 5'-guanylylimidodiphosphate (Gpp(NH)p; a nonhydrolysable guanine nucleotide analog which bypasses the receptors and directly activates G proteins) stimulated [3H]2-deoxy-D-glucose (2DG) uptake by C6 cells, suggesting that hexose uptake is a G protein-mediated process. To identify the G protein involved in glucose uptake by C6 cells, the effect of carbachol on 2DG uptake was examined in the presence of pertussis toxin. Pertussis toxin treatment did not alter the ability of C6 cells to respond to carbachol, ruling out the involvement of G(i alpha) in 2DG uptake. C6 cells were transfected with G(q alpha) or GLUT1 cDNA for 48 h, exposed to 1 mM carbachol for 2 h, and processed for 2DG uptake. Carbachol stimulated 2DG uptake in both G(q alpha) and GLUT1-transfected cells. Gpp(NH)p, also stimulated 2DG uptake in G(q alpha) and GLUT1-transfected cells. These results suggest that muscarinic receptor coupling to G(q alpha) regulates hexose uptake in C6 cells.