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.