Increased vascular permeability is another characteristic vascular abnormality in diabetic patients and animals, in which increased permeability can occur at as early as 4-6 weeks' duration of diabetes, suggesting endothelial cell dysfunctions (139). Because the vascular barrier is formed by tight junctions between endothelial cells, the increase in permeability as a result of the abnormalities in the endothelial cells. The activation PKC can directly increase the permeability of albumin and other macromolecules through barriers formed by endothelial cells, probably by phosphorylating the cytoskeletal proteins forming the intercellular junctions (140-142). Recently, PKC-^1 overexpression in human dermal microvascular endothelial cells has been reported to enhance phorbol ester-induced increase in permeability to albumin (143). Thus, the actions of phorbol ester and hyperglycemia in endothelial-barrier functions are mediated in part through activation of PKC-^1 isoform.
PKC activation can also regulate vascular permeability and neovascularization via the expression of growth factors, such as VEGF/vascular permeability factor (VPF), which is increased in ocular fluids from diabetic patients and has been implicated in the neovascularization process of proliferative retinopathy (144). We have reported that both the mitogenic and permeability-induced actions of VEGF/VPF are partly as a result of the activation of PKC^ via the tyrosine phosphorylation of phospholipase-8 (145). The use of the PKCP selective inhibitor LY333531 can decrease endothelial cell proliferation, angiogenesis, and permeability induced by VEGF (145,146).
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All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.