Cw. Heilig et al., Antisense GLUT-1 protects mesangial cells from glucose induction of GLUT-1and fibronectin expression, AM J P-REN, 280(4), 2001, pp. F657-F666
A stable clone of rat mesangial cells expressing antisense GLUT-1 (i.e., MC
GT1AS cells) was developed to protect them from high glucose exposure. GLUT
-1 protein was reduced 50%, and the 2-deoxy-[H-3] glucose uptake rate was r
educed 33% in MCGT1AS. MCLacZ control cells and MCGT1 GLUT-1-overexpressing
cells were used for comparisons. In MCLacZ, 20 mM D-glucose increased GLUT
-1 transcription 90% vs. no increase in MCGT1AS. Glucose (8 mM) and 12 mM x
ylitol [a hexose monophosphate (HMP) shunt substrate] did not stimulate GLU
T-1 transcription. An 87% replacement of the standard 8 mM D-glucose with 3
-O-methylglucose reduced GLUT-1 transcription 80%. D-Glucose (20 mM) increa
sed fibronectin mRNA and protein by 47 and 100%, respectively, in MCLacZ vs
. no increases in MCGT1AS. Fibronectin synthesis was elevated 48% in MCGT1
and reduced 44% in MCGT1AS. We conclude that 1) transcription of GLUT-1 in
response to D-glucose depends on glucose metabolism, although not through t
he HMP shunt, and 2) antisense GLUT-1 treatment of mesangial cells blocks D
-glucose-induced GLUT-1 and fibronectin expression, thereby demonstrating a
protective effect that could be beneficial in the setting of diabetes.