ANGIOTENSIN-II INCREASES GLUCOSE-UPTAKE AND GLUCOSE TRANSPORTER-1 MESSENGER-RNA LEVELS IN ASTROGLIA

In this study, we have investigated the effects of angiotensin II (ANG II) on glucose uptake into astroglia cultured from adult rat hypothalamus and brain stem. ANG II (30 min to 4 h; 10(-9) to 10(-6) M) stimulated time- and concentration-dependent increases in the uptake of 2-deoxy-D-[H-3]glucose into cultured astroglia. This effect of ANG II (10(-7) M) is via AT(1) receptors and protein kinase C (PKC), since it was inhibited by losartan (10(-6) M) and staurosporine (10(-6) M), respectively. Furthermore, this ANG II action was inhibited by both cycloheximide (1 mu g/ml) and actinomycin D (10(-6) M), indicating that synthesis of new glucose transporters is involved. This was confirmed by the finding that ANG II (30 min to 4 h; 10(-9) to 10(-5) M) stimulated time- and concentration-dependent increases in the steady-state levels of glucose transporter-1 (GLUT-1) mRNA in these cultures. In addition, the increase in steady-state levels of GLUT-1 mRNA elicited by ANG II was mediated by AT(1) receptors and PKC. These data suggest that ANG II stimulates glucose uptake into cultured astroglia via a path way that involves AT(1) receptors, PKC, and increased steady-state levels of GLUT-1 mRNA.