Diabetic retinopathy is known to be worsened when
hypoglycemia occurs, however the pathogenic mechanisms are not defined.
Vascular endothelial growth factor (
VEGF) is increased in ocular fluid with
diabetic retinopathy and linked with development of retinopathy. In this study, we examined whether
glucose deficiency could up-regulate
VEGF levels in
retinal pigmented cells. Exposure to
glucose deprived medium induced 30% up-regulation of
VEGF mRNA. In
hypoxia, as one of the most well-known inducer of
VEGF, its up-regulation mechanism is mainly due to increase of transcription of
VEGF gene via
hypoxia response element in 5'-untranslated region (5'-UTR). We examined the role of 5'-UTR and 3'-UTR of
VEGF gene in
glucose deprived conditions using
luciferase assay system. 5'-UTR containing reporter vector did not show increase of activity in
glucose deprived conditions in contrast to the result in
oxygen deprived condition. Both 5'-UTR and 3'-UTR containing vector demonstrated significant increase of activity in
glucose deficient conditions compared with 5'-UTR containing vector. These findings suggest 3'-UTR of
VEGF gene is important for increasing
mRNA level in
glucose deprived condition.