Ruboxistaurin, a protein kinase C β inhibitor, as an emerging treatment for diabetes microvascular complications

Annals of Pharmacotherapy

Volumn 39, Issue 10, 2005, Pages 1693-1699

  Joy, Scott V ^a   Scates, Ann C ^b   Bearelly, Srilaxmi ^a   Dar, Moahad ^a   Taulien, Christina A ^a   Goebel, Jason A ^a   Cooney, Michael J ^a  

^a DUKE UNIVERSITY MEDICAL CENTER   (United States)

^b DUKE UNIVERSITY HOSPITAL   (United States)

Author keywords

Diabetic microvascular complications; LY333531; Protein kinase C; Ruboxistaurin

Indexed keywords

ALDOSE REDUCTASE INHIBITOR; GROWTH FACTOR; HORMONE; ISOENZYME; NZ 314; PROTEIN KINASE C BETA; PROTEIN KINASE C BETA1; PROTEIN KINASE C BETA2; PROTEIN KINASE C INHIBITOR; QUINIDINE; RUBOXISTAURIN; UNCLASSIFIED DRUG;

CLINICAL TRIAL; DIABETES MELLITUS; DIABETIC ANGIOPATHY; DIABETIC NEPHROPATHY; DIABETIC NEUROPATHY; DIABETIC RETINOPATHY; DISEASE COURSE; DRUG MECHANISM; DRUG SELECTIVITY; ENZYME ACTIVATION; ENZYME INHIBITION; HUMAN; NONHUMAN; PRIORITY JOURNAL; RAT; REVIEW; SIGNAL TRANSDUCTION; STIMULUS RESPONSE; TREATMENT OUTCOME;

ANIMALS; CLINICAL TRIALS; DIABETIC ANGIOPATHIES; DIABETIC NEPHROPATHIES; DIABETIC NEUROPATHIES; ENZYME INHIBITORS; HUMANS; INDOLES; MALEIMIDES; MEDLINE; PROTEIN KINASE C; TREATMENT OUTCOME;

EID: 25844456960     PISSN: 10600280     EISSN: None     Source Type: Journal    
DOI: 10.1345/aph.1E572     Document Type: Review

References (63)

1. King H, Aubert RE, Herman WH. Global burden of diabetes, 1995-2005: prevalence, numerical estimates, and projections. Diabetes Care 1998;21:1414-31.
2. Ruigomez A, Garcia Rodriguez LA. Presence of diabetes related complications at the time of NIDDM diagnosis: an important prognostic factor. Eur J Epidemiol 1998;14:439-45.
3. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998;352:837-63.
4. Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329:977-86.
5. Way KJ, Katai N, King GL. Protein kinase C and the development of diabetic vascular complications. Diabet Med 2001;18:945-59.
6. Xia P, Inoguchi T, Kern TS, Engerman RL, Oates PJ, King GL. Characterization of the mechanism for the chronic activation of diacylglycerol-protein kinase C pathway in diabetes and hypergalactosemia. Diabetes 1994;43:1122-9.
7. Sheetz MJ, King GL. Molecular understanding of hyperglycemia's adverse effects for diabetic complications. JAMA 2002;288:2579-88.
8. Nishikawa T, Edelstein D, Du XL, Yamagishi S, Matsumura T, Kaneda Y, et al. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 2000;404:787-90.
9. Du XL, Edelstein D, Rossetti L, Fantus IG, Goldberg H, Ziyadeh F, et al. Hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation. Proc Natl Acad Sci U S A 2000;97:12222-6.
10. Way KJ, Chou E, King GL. Identification of PKC-isoform-specific biological actions using pharmacological approaches. Trends Pharmacol Sci 2000;21:181-7.
11. Ohno S, Nishizuka Y. Protein kinase C isotypes and their specific functions: prologue. J Biochem 2002;132:509-11.
12. Dutil EM, Newton AC. Dual role of pseudosubstrate in the coordinated regulation of protein kinase C by phosphorylation and diacylglycerol. J Biol Chem 2000;275:10697-701.
13. Idris I, Gray S, Donnelly R. Protein kinase C activation: isozyme-specific effects on metabolism and cardiovascular complication in diabetes. Diabetologia 2001;44:659-73.
14. Liu WS, Heckman CA. The sevenfold way of PKC regulation. Cell Signal 1998;10:529-42.
15. Tomlinson DR. Mitogen-activated protein kinases as glucose transducers for diabetic complications. Diabetologia 1999;42:1271-81.
16. Wolf BA, Williamson JR, Easom RA, Chang K, Sherman WR, Turk J. Diacylglycerol accumulation and microvascular abnormalities induced by elevated glucose levels. J Clin Invest 1991;87:31-8.
17. Scivittaro V, Ganz MB, Weiss MF. AGEs induce oxidative stress and activate protein kinase C-beta (II) in neonatal mesangial cells. Am J Physiol Renal Physiol 2000;278:F676-83.
18. Aronson D, Rayfield EJ. How hyperglycemia promotes atherosclerosis: molecular mechanisms. Cardiovasc Diabetol 2002;1:1.
19. Burkey JL, Campanale KM, O'Bannon DD. Cramer JW, Farid NA. Disposition of LY333531, a selective protein kinase C beta inhibitor, in the Fischer 344 rat and beagle dog. Xenobiotica 2002;32:1045-52.
20. Ring BJ, Gillespie JS, Binkley SN, Campanale KM, Wrighton SA. The interaction of a selective protein kinase C beta inhibitor with the human cytochrome P450. Drug Metab Dispos 2002;30:957-61.
21. Demolle D, DeSuray JM, Onkelinx C. Pharmacokinetics and safety of multiple oral doses of LY333531, a PKC β inhibitor, in healthy subjects (abstract). Clin Pharmacol Ther 1999;65:189.
22. Kempen JH, O'Colmain BJ, Leske MC, Haffner SM, Klein R, Moss SE, et al. The prevalence of diabetic retinopathy among adults in the United States. Arch Ophthalmol 2004;122:552-63.
23. Klein R, Klein BEK, Moss SE, Davis MD, DeMets DL. The Wisconsin epidemiologic study of diabetic retinopathy. II. Prevalence and risk of diabetic retinopathy when age at diagnosis is less than 30 years. Arch Ophthalmol 1984;102:520-6.
24. Ishii H, Koya D, King GL. Protein kinase C activation and its role in the development of vascular complications in diabetes mellitus. J Mol Med 1998;76:21-31.
25. Koya D, King GL. Protein kinase C activation and the development of diabetic complications. Diabetes 1998;47:859-66.
26. Frank RN. Potential new medical therapies for diabetic retinopathy: protein kinase C inhibitors. Am J Ophthalmol 2002;133:693-8.
27. Witmer AN, Vrensen GF, Van Noorden CJ, Schlingemann RO. Vascular endothelial growth factors and angiogenesis in eye disease. Prog Retin Eye Res 2003;22:1-29.
28. Yokota T, Ma RC, Park JY, Isshiki K, Sotiropoulos KB, Rauniyar RK, et al. Role of protein kinase C on the expression of platelet-derived growth factor and endothelin-1 in the retina of diabetic rats and cultured retinal capillary pericytes. Diabetes 2003;52:838-45.
29. Ishii H, Jirousek MR, Koya D, Takagi C, Xia P, Clermont A, et al. Amelioration of vascular dysfunctions in diabetic rats by an oral PKC β inhibitor. Science 1996;272:728-31.
30. Xia P, Aiello LP, Ishii H, Jiang ZY, Park DJ, Robinson GS, et al. Characterization of vascular endothelial growth factors effect on the activation of protein kinase C, its isoforms, and endothelial cell growth. J Clin Invest 1996;98:2018-26.
31. Danis RP, Bingaman DP, Jirousek M, Yang Y. Inhibition of intraocular neovascularization caused by retinal ischemia in pigs by PKC β inhibition with LY333531. Invest Ophthalmol Vis Sci 1998;39:171-9.
32. Suzuma K, Takahara N, Suzuma I, Isshiki K, Ueki K, Leitges M, et al. Characterization of protein kinase C β isoforms action on retinoblastoma protein phosphorylation, vascular endothelial growth factor-induced endothelial cell proliferation, and retinal neovascularization. Proc Natl Acad Sci U S A 2002;99:721-6.
33. Aiello LP, Bursell S, Devries T. Protein kinase C β selective inhibitor LY333531 ameliorates abnormal retinal hemodynamics in patients with diabetes (abstract). Diabetes 1999;48:A19.
34. Aiello LP. Medical and pharmacologic treatment of diabetic macular edema. Presented at: The American Academy of Ophthalmology: Retina Subspecialty Days. Anaheim, CA, November 15-18, 2003.
35. The PKC-DRS Study Group. The effect of ruboxistaurin on visual loss in patients with moderately severe to very severe nonproliferative diabetic retinopathy: initial results of the protein kinase C beta inhibitor diabetic retinopathy study (PKC-DRS) multicenter randomized clinical trial. Diabetes 2005;54:2188-97.
36. Donnelly R, Idris I, Forrester JV. Protein kinase C inhibition and diabetic retinopathy: a shot in the dark at translational research. Br J Ophthalmol 2004;88:145-51.
37. Duby JJ, Campbell RK, Setter SM, White JR, Rasmussen KA. Diabetic neuropathy: an intensive review. Am J Health Syst Pharm 2004;61:160-76.
38. Vinik AI, Park TS, Stansberry KB, Pittenger GL. Diabetic neuropathies. Diabetologia 2000;43:957-73.
39. Cameron NE, Eaton SE, Cotter MA, Tesfaye S. Vascular factors and metabolic interactions in the pathogenesis of diabetic neuropathy. Diabetologia 2001;44:1973-88.
40. Vileikyte L, Peyrot M, Bundy C, Rubin RR, Leventhal H, Mora P, et al. The development and validation of a neuropathy- and foot ulcer-specific quality of life instrument. Diabetes Care 2003;26:2549-55.
41. Ziegler D. Cardiovascular autonomic neuropathy: clinical manifestations and measurement. Diabetes Rev 1999;7:342-57.
42. Vinik A, Erbas T. Recognizing and treating diabetic autonomic neuropathy. Cleve Clin J Med 2001;68:928-44.
43. Vinik AI, Erbas T, Stansberry K. Gastrointestinal, genitourinary, and neurovascular disturbances in diabetes. Diabetes Rev 1999;7:3758-81.
44. Perkins BA, Olaleye D, Zinman B, Bril V. Simple screening tests for peripheral neuropathy in the diabetes clinic. Diabetes Care 2001;24:250-6.
45. Apelqvist J, Bakker K, van Houtum WH, Nabuurs-Franssen MH, Schaper NC. International consensus and practical guidelines on the management and prevention of the diabetic foot. International Working Group on the Diabetic Foot. Diabetes Metab Res Rev 2000;16(suppl 1):S84-92.
46. Gianni C, Dyck PJ. Basement membrane thickening and perocyte degeneration precede development of diabetic polyneuropathy and are associated with its severity. Ann Neurol 1995;37:498-504.
47. Britland ST, Young RJ, Sharma AK, Clarke BF. Relationship of endoneurial capillary abnormalities to type and severity of diabetic polyneuropathy. Diabetes 1990;39:909-13.
48. Timperley WR, Ward JD, Preston FE, Duckworth T, O'Malley BC. A reassessment of vascular factors in relation to intravascular coagulation. Diabetologia 1976;12:237-43.
49. Eichberg J. Protein kinase C changes in diabetes: is the concept relevant to neuropathy? Int Rev Neurobiol 2002;50:61-82.
50. Cameron NE, Cotter MA, Jack AM, Basso MD, Hohman TC. Protein kinase C effects on nerve function, perfusion, Na(+), K(+)-ATPase activity and glutathione content in diabetic rats. Diabetologia 1999;42:1120-30.
51. Nakamura J, Kato K, Hamada Y, Nakayama M, Chaya S, Nakashima E, et al. A protein kinase C-β-selective inhibitor ameliorates neural dysfunction in streptozotocin-induced diabetic rats. Diabetes 1999;48:2090-5.
52. Litchy W, Dyck P, Tesfaye S, Zhang D, Bastyr E, The MBBQ Study Group. Diabetic peripheral neuropathy assessed by neurological examination and composite scores is improved with L333531 treatment. In: Program and abstracts of the 62nd Scientific Sessions of the American Diabetes Association. San Francisco, CA, June 14-18, 2002. Poster 800-P. Diabetes 2002;51:(suppl 2):A197.
53. Vinik A, Tesfaye S, Zhang D, Bastyr E, The MBBQ Study Group. LY3333531 treatment improves diabetic peripheral neuropathy with symptoms (abstract 321-OR). Program and abstracts of the 62nd Scientific Sessions of the American Diabetes Association. San Francisco, CA, June 14-18, 2002. Diabetes 2002;51(suppl):2.
54. Mogensen CE. Microalbuminuria, blood pressure and diabetic renal disease: origin and development of ideas. Diabetologia 1999;42:263-85.
55. Whiteside CI, Dlugosz JA. Mesangial cell protein kinase C isozyme activation in the diabetic milieu. Am J Physiol Renal Physiol 2002;282: F975-80.
56. Cooper ME. Pathogenesis, prevention, and treatment of diabetic nephropathy. Lancet 1998;352:213-9.
57. Kang DH, Johnson RJ. Vascular endothelial growth factor: a new player in the pathogenesis of renal fibrosis. Curr Opin Nephrol Hypertens 2003;12:43-9.
58. Bailey E, Bottomley MJ, Westwell S, Pringle JH, Furness PN, Feehally J, et al. Vascular endothelial growth factor mRNA expression in minimal change, membranous, and diabetic nephropathy demonstrated by non-isotopic in situ hybridization. J Clin Pathol 1999;52:735-8.
59. Makino H, Tanaka I, Mukoyama M, Sugawara A, Mori K, Muro S, et al. Prevention of diabetic nephropathy in rats by prostaglandin E receptor EP1-selective antagonist. J Am Soc Nephrol 2002;13:1757-65.
60. Dunlop ME, Clark S, Mahadevan P, Muggli E, Larkins RG. Production of hyaluronan by glomerular mesangial cells in response to fibronectin and platelet-derived growth factor. Kidney Int 1996;50:40-4.
61. Tuttle KR, Anderson PW. A novel potential therapy for diabetic nephropathy and vascular complications: protein kinase C β inhibition. Am J Kidney Dis 2003;42:456-65.
62. Koya D, Haneda M, Nakagawa H, Isshiki K, Sato H, Maeda S, et al. Amelioration of accelerated diabetic mesangial expansion by treatment with a PKC β inhibitor in diabetic db/db mice, a rodent model for type 2 diabetes. FASEB J 2000;14:439-47.
63. Tuttle KT, Bakris GL, Toto RD, McGill JB, Hu K, Anderson PW. Effect of raboxistaurin on albuminuria and GFR in persons with type 2 diabetes and nephropathy (abstract). Diabetes 2005;54(suppl 1):223.