REGULATION OF N-3 AND N-6 FATTY-ACID METABOLISM IN RETINAL AND CEREBRAL MICROVASCULAR ENDOTHELIAL-CELLS BY HIGH GLUCOSE

The present study was undertaken to determine whether polyunsaturated fatty acid metabolism is affected by high glucose levels in cerebral a nd retinal microvascular endothelial cells. The metabolism of [3-C-14] 22:5n-3 and [1-C-14]18:2n-6 was studied in cells previously cultured f or 5 days in normal (5 mM) or high (30 mM) glucose medium, After incub ation of retinal endothelial cells with [3-C-14]22:5n-3 in the high gl ucose condition, the formation of labeled 24:6n-3 and 22:6n-3 was incr eased, and that of labeled 24:5n-3 was decreased, compared with the no rmal glucose condition. The changes were found for fatty acids esterif ied in cellular lipids and those released into the medium, After incub ation with [1-C-14]18:2n-6, levels of all elongation/desaturation prod ucts were increased at the expense of the precursor in retinal endothe lial cells cultured in high glucose medium, The changes were primarily found for esterified fatty acids, with the release of n-6 fatty acids being minor in both glucose concentrations. By contrast, high glucose levels did not affect the metabolism of [3-C-14]22:5n-3 and [1-C-14] 18:2n-6 in cerebral endothelial cells. The changes in metabolic activi ty of retinal endothelial cells were not reflected in the fatty acid c omposition, The present data suggest that high glucose can increase th e desaturation process in retinal but not cerebral endothelial cells. This may produce some lipid abnormalities in retinal microvasculature and contribute to altered vascular function observed in diabetic retin opathy.