Publication Date:
1996-05-03
Description:
The vascular complications of diabetes mellitus have been correlated with enhanced activation of protein kinase C (PKC). LY333531, a specific inhibitor of the beta isoform of PKC, was synthesized and was shown to be a competitive reversible inhibitor of PKC beta 1 and beta 2, with a half-maximal inhibitory constant of approximately 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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ishii, H -- Jirousek, M R -- Koya, D -- Takagi, C -- Xia, P -- Clermont, A -- Bursell, S E -- Kern, T S -- Ballas, L M -- Heath, W F -- Stramm, L E -- Feener, E P -- King, G L -- DK36836/DK/NIDDK NIH HHS/ -- EY05110-11/EY/NEI NIH HHS/ -- New York, N.Y. -- Science. 1996 May 3;272(5262):728-31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Research Division, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02215, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8614835" target="_blank"〉PubMed〈/a〉
Keywords:
Administration, Oral
;
Albuminuria/prevention & control
;
Animals
;
Diabetes Mellitus, Experimental/*complications/enzymology/physiopathology
;
Diabetic Angiopathies/enzymology/etiology/*prevention & control
;
Diglycerides/metabolism
;
Dose-Response Relationship, Drug
;
Enzyme Activation
;
Enzyme Inhibitors/chemistry/*pharmacology
;
Glomerular Filtration Rate/drug effects
;
Humans
;
Indoles/administration & dosage/chemistry/*pharmacology
;
Isoenzymes/*antagonists & inhibitors/metabolism
;
Kidney Glomerulus/metabolism
;
Male
;
Maleimides/administration & dosage/chemistry/*pharmacology
;
Muscle, Smooth, Vascular/enzymology
;
Phosphorylation/drug effects
;
Protein Kinase C/*antagonists & inhibitors/metabolism
;
Protein Kinase C beta
;
Rats
;
Rats, Sprague-Dawley
;
Regional Blood Flow/drug effects
;
Renal Plasma Flow/drug effects
;
Retina/metabolism
;
Retinal Vessels/physiopathology
;
Substrate Specificity
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
