CORRELATION OF DIACYLGLYCEROL LEVEL AND PROTEIN-KINASE-C ACTIVITY IN RAT RETINA TO RETINAL CIRCULATION

The increases in diacylglycerol (DAG) level and protein kinase C (PKC) activity have been characterized biochemically and functionally in th e retina and the brain of diabetic rats as well as in cultured vascula r cells. PKC specific activities were increased in the membraneous fra ction of retina from streptozotocin (STZ)-induced diabetic rats and th e genetically determined diabetic BB rats, respectively, after 1 or 2 wk of diabetes, compared with control. The ratio of total PKC activiti es from membraneous and cytosol fractions was also increased in the re tina of diabetic rats. With diabetes, all the isoenzymes and the total DAG level were increased in the rat retina, whereas no changes were f ound in the rat brain. Insulin treatment normalized plasma glucose lev els and partially prevented the increases in the membraneous PKC activ ity and all the isoenzymes in the retina. In the retinal endothelial c ells, the total DAG level and PKC specific activities are increased by 36 and 22%, respectively, in the membraneous pool when the glucose le vels are changed from 5.5 to 22 mM. Activation of PKC activity and iso form betaII by the vitreal injection of phorbol dibutyrate mimicked th e abnormal retinal blood circulation observed in diabetic rats (2.22 /- 0.24 vs. 1.83 +/- 0.40 s). Thus diabetes and elevated glucose level s will increase DAG level and PKC activities and its isoenzyme specifi cally in vascular cells and may affect retinal hemodynamics.