Fig. 7

IMCD cells incubated with HG upregulate GLUT1 enabling glucose uptake. HG increases PRR synthesis along with prorenin and renin secretion in cell culture mediate. The specific GLUT1 inhibitor, BAY 876, impairs the induction of PRR, prorenin, and renin. Increases in intracellular ROS during HG conditions are attenuated by GLUT1 blockade, while the induction of TGF-β and CTGF in HG is effectively blunted by BAY876. PRO20, a PRR blocker, impairs TGF-β induction but did not prevent increases in intracellular ROS and CTGF protein expression. Treatment with ROS scavenger p-coumaric acid impairs intracellular ROS concomitant with impairment of CTGF upregulation. Intracellular ROS formation from glucose exposure or uptake may likely mediate CTGF induction which also may be sustained by TGF-β receptor in the long term. Long term effects of HG may be also related to modification of the activity of NOX4 as suggested by our previous reports. Oxidative effects of HG-dependent uptake may be also related with other suggested transporters expressed in collecting duct cells (not studied here) such as GLUT12