J Tang1, X W Zhu, W D Lust, T S Kern. 1. Center for Diabetes Research and Department of Medicine, Case Western Reserve University, Cleveland, Ohio 44106-4951, USA.
Abstract
AIMS/HYPOTHESIS: The retina is embryologically similar to cerebral cortex and the tissues of both are exposed to similar blood glucose concentrations. Nevertheless, in diabetes the retina develops metabolic abnormalities and microvascular lesions from which cerebrum seems relatively protected. We directly compared glucose concentrations and expression of GLUT-1 (the major carrier transporting glucose from blood into the neural retina and cerebrum) in the two tissues from normal and diabetic rats. METHODS: Tissue and intracellular glucose were measured using two methods: direct assay of glucose and assay of Amadori products on intracellular proteins. The expression of GLUT-1 was measured using western blots in tissue and in the isolated endothelial luminal membrane of the two vascular beds. RESULTS: Both methods assessing intracellular glucose indicate that intracellular concentrations of glucose in diabetes increased significantly in the retina but not in cerebral cortex. Concentrations of free glucose and Amadori product in retinas of diabetic animals were increased above normal by 334% and 122%, respectively, whereas there was no statistically significant increase in either parameter in the cerebral cortex of diabetic animals. In contrast to the observed increase in glucose in the retina in diabetes, expression of GLUT-1 on the luminal plasmalemma of the retinal vascular endothelium and in homogenates of whole retina decreased to a statistically significant extent (55% and 36%, respectively compared to normal). In the luminal cell membrane of the cerebral vasculature, diabetes did not decrease expression of GLUT-1 but tended to increase it slightly. CONCLUSIONS/ INTERPRETATION: Even among tissues that do not require insulin for glucose uptake, tissue glucose concentration varies in diabetes. The greater increase in glucose concentration in retina than in cerebrum in diabetes probably contributes to the tissue differences in biochemical and histopathologic sequelae of the disease. The expression of GLUT-1 in the microvasculature is unlikely to account for the differences in tissue glucose between retina and cerebrum.
AIMS/HYPOTHESIS: The retina is embryologically similar to cerebral cortex and the tissues of both are exposed to similar blood glucose concentrations. Nevertheless, in diabetes the retina develops metabolic abnormalities and microvascular lesions from which cerebrum seems relatively protected. We directly compared glucose concentrations and expression of GLUT-1 (the major carrier transporting glucose from blood into the neural retina and cerebrum) in the two tissues from normal and diabeticrats. METHODS: Tissue and intracellular glucose were measured using two methods: direct assay of glucose and assay of Amadori products on intracellular proteins. The expression of GLUT-1 was measured using western blots in tissue and in the isolated endothelial luminal membrane of the two vascular beds. RESULTS: Both methods assessing intracellular glucose indicate that intracellular concentrations of glucose in diabetes increased significantly in the retina but not in cerebral cortex. Concentrations of freeglucose and Amadori product in retinas of diabetic animals were increased above normal by 334% and 122%, respectively, whereas there was no statistically significant increase in either parameter in the cerebral cortex of diabetic animals. In contrast to the observed increase in glucose in the retina in diabetes, expression of GLUT-1 on the luminal plasmalemma of the retinal vascular endothelium and in homogenates of whole retina decreased to a statistically significant extent (55% and 36%, respectively compared to normal). In the luminal cell membrane of the cerebral vasculature, diabetes did not decrease expression of GLUT-1 but tended to increase it slightly. CONCLUSIONS/ INTERPRETATION: Even among tissues that do not require insulin for glucose uptake, tissue glucose concentration varies in diabetes. The greater increase in glucose concentration in retina than in cerebrum in diabetes probably contributes to the tissue differences in biochemical and histopathologic sequelae of the disease. The expression of GLUT-1 in the microvasculature is unlikely to account for the differences in tissue glucose between retina and cerebrum.
Authors: Ahmed S Ibrahim; Azza B El-Remessy; Suraporn Matragoon; Wenbo Zhang; Yogin Patel; Sohail Khan; Mohammed M Al-Gayyar; Mamdouh M El-Shishtawy; Gregory I Liou Journal: Diabetes Date: 2011-02-11 Impact factor: 9.461