Protein kinase C inhibitors in the treatment and prevention of diabetic complications

Diabetic complications are known to be associated with activation of the protein kinase C pathway through the de novo synthesis of diacylglycerol. Multiple studies have reported that the activation of protein kinase C leads to increased production of extracellular matrix and cytokines and enhances contractility, permeability, and vascular cell proliferation. Specific protein kinase C isoforms, mainly the β and δ isoforms, have been shown to be persistently activated in diabetes mellitus. The gene for selective protein kinase C inhibition, LY333531, has been shown to prevent or reverse various vascular dysfunctions in vitro and in vivo. Clinical trials are now ongoing to evaluate the effect of LY333531 on pathologic changes in cardiovascular disease, diabetic retinopathy, neuropathy, and peripheral vascular disease.