Amelioration of Vascular Dysfunctions in Diabetic Rats by an Oral PKC β Inhibitor

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Science  03 May 1996:
Vol. 272, Issue 5262, pp. 728-731
DOI: 10.1126/science.272.5262.728


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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