PT - JOURNAL ARTICLE AU - Ishii, Hidehiro AU - Jirousek, Michael R. AU - Koya, Daisuke AU - Takagi, Chikako AU - Xia, Pu AU - Clermont, Allen AU - Bursell, Sven-Erik AU - Kern, Timothy S. AU - Ballas, Lawrence M. AU - Heath, William F. AU - Stramm, Lawrence E. AU - Feener, Edward P. AU - King, George L. TI - Amelioration of Vascular Dysfunctions in Diabetic Rats by an Oral PKC β Inhibitor AID - 10.1126/science.272.5262.728 DP - 1996 May 03 TA - Science PG - 728--731 VI - 272 IP - 5262 4099 - http://science.sciencemag.org/content/272/5262/728.short 4100 - http://science.sciencemag.org/content/272/5262/728.full SO - Science1996 May 03; 272 AB - The vascular complications of diabetes mellitus have been correlated with enhanced activation of protein kinase C (PKC). LY333531, a specific inhibitor of the β isoform of PKC, was synthesized and was shown to be a competitive reversible inhibitor of PKC β1 and β2, with a half-maximal inhibitory constant of ∼5 nM; this value was one-fiftieth of that for other PKC isoenzymes and one-thousandth of that for non-PKC kinases. When administered orally, LY333531 ameliorated the glomerular filtration rate, albumin excretion rate, and retinal circulation in diabetic rats in a dose-responsive manner, in parallel with its inhibition of PKC activities.