Amelioration of vascular dysfunctions in diabetic rats by an oral PKC β inhibitor
H Ishii, MR Jirousek, D Koya, C Takagi, P Xia… - Science, 1996 - science.org
H Ishii, MR Jirousek, D Koya, C Takagi, P Xia, A Clermont, SE Bursell, TS Kern, LM Ballas…
Science, 1996•science.orgThe 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 …
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 …
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.
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