Stimulation of GLUT-1 glucose transporter expression in response to hyperosmolarity

Glucose transporter isoform-1 (GLUT-1) expression is stimulated in response to stressful conditions. Here we examined the mechanisms mediating the enh anced expression of GLUT-1 by hyperosmolarity. GLUT-1 mRNA, GLUT-1 protein, and glucose transport increased after exposure of Clone 9 cells to 600 mos mol/l (produced by addition of mannitol). The stimulation of glucose transp ort was biphasic: in the early phase (0-6 h) a similar to2.5-fold stimulati on of glucose uptake was associated with no change in the content of GLUT-1 mRNA, GLUT-1 protein, or GLUT-1 in the plasma membrane, whereas the simila r to 17-fold stimulation of glucose transport during the late phase (12-24 h) was associated with increases in both GLUT-1 mRNA (similar to7.5-fold) a nd GLUT-1 protein content. Cell sorbitol increased after 3 h of exposure to hyperosmolarity. The increase in GLUT-1 mRNA content was associated with a n increase in the half-life of the mRNA from 2 to 8 h. A 44-bp region in th e proximal GLUT-1 promoter was necessary for basal activity and for the two - to threefold increases in expression by hyperosmolarity. It is concluded that the increase in GLUT-1 mRNA content is mediated by both enhanced trans cription and stabilization of GLUT-1 mRNA and is associated with increases in GLUT-1 content and glucose transport activity.