Best Practice & Research Clinical Endocrinology & Metabolism
Volume 21, Issue 4 , Pages 573-586 , December 2007

PKC inhibition and diabetic microvascular complications

  • Margaret Clarke, MBChB (Hons), MRCP (Consultant Physician, Diabetes and Endocrinology)

      Affiliations

    • Corresponding Author InformationCorresponding author. Tel.: +44 121 4242104.
    • ,
  • Paul M. Dodson, MD, FRCP, FRCOphth (Consultant Physician, Diabetes and Medical Ophthalmology)

References 

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  8. Donnelly R. Protein kinase C: a novel therapeutic target in microvascular complications. Modern Diabetes Management. 2000;1(1):13–16
  9. King GL. The role of hyperglycaemia and hyperinsulinaemia in causing vascular dysfunction in diabetes. Annals of Medicine. 1996;28:427–432
  10. Tolentino MJ, Miller JW, Gragoudas ES, et al. Intravitreous injections of vascular endothelial growth factor produce retinal ischaemia and microangiopathy in an adult primate. Ophthalmology. 1996 Nov;103(11):1820–1828
  11. Xia P, Aiello LP, Ishii H, et al. Characterization of vascular endothelial factor's effect on the activation of protein kinase C, its isoforms, and endothelial cell growth. The Journal of Clinical Investigation. 1996;98(9):2018–2026
  12. Demolle D, de Suray JM, Onkelinx C. Pharmacokinetics and safety of multiple oral doses of LY333531, a PKC beta inhibitor, in healthy subjects. Clinical Pharmacology and Therapeutics. 1999;65:189
  13. Demolle D, de Suray JM, Vandenhende F, et al. LY333531 single escalating oral dose study in healthy volunteers. Diabetologia. 1998;41(supplement 1):A354
  14. Aiello LP, Clermont A, Arora V, et al. Inhibition of PKC beta by oral administration of ruboxistaurin is well tolerated and ameliorates diabetes-induced retinal hemodynamic abnormalities in patients. Investigative Ophthalmology & Visual Science. 2006;47:86–92
  15. The PKC-DRS Study Group . The effect of ruboxistaurin on visual loss in patients with moderately severe to very severe non-proliferative diabetic retinopathy: initial results of the PKC-DRS multicenter randomized clinical trial. Diabetes. 2005;54:2188–2197
  16. The PKC-DMES Study Group . Effect of ruboxistaurin in patients with diabetic macular edema: 30 month results of the randomized PKC-DMES clinical trial. Archives of Ophthalmology. 2007;125(3):318–324
  17. The PKC-DRS2 Study Group . The effect of ruboxistaurin on visual loss in patients with diabetic retinopathy. Ophthalmology. 2006;113:2221–2230
  18. Walton C, Ryder REJ, Girach A. Protein kinase C inhibition in diabetic retinopathy and microvascular disease. Practical Diabetes International. 2007;24(5):263–268
  19. Ishii H, Jirousek MR, Koya D, et al. Amelioration of vascular dysfunctions in diabetic rats by an oral PKC β inhibitor. Science. 1996;272:728–731
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  22. Vinik AI, Bril V, Kemplar P, et al. Treatment of symptomatic diabetic peripheral neuropathy with the protein kinase C beta-inhibitor ruboxistaurin mesylate during a 1 year, randomized, placebo-controlled, double-blind clinical trial. Clinical Therapeutics. 2005;27(8):1164–1180
  23. McGill J, King G, Berg P, et al. Clinical safety of the selective PKC-β inhibitor, ruboxistaurin. Expert Opinion on Drug Safety. 2006;5(6):835–845
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PII: S1521-690X(07)00091-7

doi: 10.1016/j.beem.2007.09.007

Best Practice & Research Clinical Endocrinology & Metabolism
Volume 21, Issue 4 , Pages 573-586 , December 2007

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