Amelioration of vascular dysfunctions in diabetic rats by an oral PKC β inhibitor

Science

Volumn 272, Issue 5262, 1996, Pages 728-731

  Ishii, Hidehiro ^a   Jirousek, Michael R ^b   Koya, Daisuke ^a   Takagi, Chikako ^a   Xia, Pu ^a   Clermont, Allen ^a   Bursell, Sven Erik ^a   Kern, Timothy S ^c   Ballas, Lawrence M ^d   Heath, William F ^b   Stramm, Lawrence E ^b   Feener, Edward P ^a   King, George L ^a  

^a JOSLIN DIABETES CENTER   (United States)

^b ELI LILLY AND COMPANY   (United States)

^c UNIVERSITY OF WISCONSIN MADISON   (United States)

^d Sphinx Pharmaceutical Corporation   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALBUMIN; PROTEIN KINASE C; PROTEIN KINASE C INHIBITOR; RUBOXISTAURIN; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; COMPETITIVE INHIBITION; CONTROLLED STUDY; DIABETES MELLITUS; DOSE RESPONSE; DRUG SYNTHESIS; ENZYME ACTIVATION; GLOMERULUS FILTRATION RATE; MALE; NONHUMAN; ORAL DRUG ADMINISTRATION; PRIORITY JOURNAL; RAT; RETINA BLOOD FLOW; URINARY EXCRETION; VASCULAR DISEASE;

ANIMALIA; GLOMERULUS;

EID: 13344293711     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.272.5262.728     Document Type: Article

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38. The rats were anesthetized with thiopental sodium (50 mg/kg intraperitoneal). Catheters were then surgically inserted in the left carotid artery (for blood sampling), the left jugular vein (for infusion), and the urinary bladder (for collection of urine) Inulin (0.6%) and PAH (1.5%) in normal saline were infused at a rate of 6.0 ml/hour for 30 min, followed by a sustained infusion of 2 0 ml/hour throughout the experiment After 60 min, two clearance studies (each 30 min) were performed in succession The concentrations of inulin and PAH were measured by the anthrone method [W H Waugh, Clin Chem 23, 639 (1977)] and the calorimetric technique [H. W Smith, N Finkelstein, L. Aliminosa, B. Crawford, M Grabor, J. Clin. Invest. 24, 388 (1945)], respectively. GFR and RPF were determined by inulin and PAH clearance, respectively, and the filtration fraction was calculated from the ratio of GFR to RPF.
39. 4, and absorbance at 492 nm was measured with a spectrophotometer. The assay range was 3 to 250 ng/ml, and the intra- and inter-assay coefficients of variation were 2 4% and 6 5%, respectively.
40. Supported by National Eye Institute grant NEI-05110-11 and Diabetes and Endocrinology Research Center grant NIDDK-36836, and partially supported by Lilly Pharmaceutical, Inc. We thank J. Davis and K. Kalter for help with the in vitro kinase assays and L Balmat for excellent secretarial assistance.