Skip to main content
SpringerLink
Log in

The Role of Protein Kinase C Activation in the Development of Diabetic Vascular Complications

  • Chapter
Endocrinology of Cardiovascular Function

Part of the book series: Endocrine Updates ((ENDO,volume 1))

Abstract

Multiple theories have been proposed to explain the pathogenesis of the various vascular complications of diabetes involving retina, glomeruli, peripheral nerves, cardiovascular tissues, wound healing and pregnancy. A few theories have emerged which can accommodate most of the data in this area (Table 1), although a single theory has not been demonstrated to explain all these changes. Extracellularly, glucose can react non-enzymatically with primary amines of proteins forming glycated compounds or oxidants (1), which can secondarily act on inflammatory cells to release cytokines or vascular cells directly via receptor or non-receptor mediated processes to cause vascular dysfunctions (2, 3).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Brownlee M, Cerami A, Vlassara H: Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications. N Engl J Med 318: 1315–1321, 1988

    Article  PubMed  CAS  Google Scholar 

  2. Vlassara H: Advanced glycation end-products and atherosclerosis. Ann Med 28: 419–426, 1996

    Article  PubMed  CAS  Google Scholar 

  3. Schmidt AM, Hori O, Cao R, Yan SD, Brett J, Wautier JL, Ogawa S, Kuwabara K, Matsumoto M, Stern D: RAGE: a novel cellular receptor for advanced glycation end products. Diabetes 45: S77–S80, 1996

    Article  PubMed  CAS  Google Scholar 

  4. Kaiser N, Sasson S, Feener EP, Boukobza-Vardi N, Higashi S, Moller DE, Davidheiser S, Przybylski RJ, King GL: Differential regulation of glucose transport and transporters by glucose in vascular endothelial and smooth muscle cells. Diabetes 42: 80–89, 1993

    Article  PubMed  CAS  Google Scholar 

  5. Greene D, Lattimer SA, Sima AAF: Sorbitol, phosphoinositides and sodium-potassium-ATPase in the pathogenesis of diabetic complications. N Engl J Med 316: 599–606, 1987

    Article  PubMed  CAS  Google Scholar 

  6. Williamson JR, Chang K, Frangos M, Hasan KS, Ido Y, Kawamura T, Nyengaard JR, Van den Enden M, Kilo C, Tilton RG: Hyperglycemic pseudohypoxia and diabetic complications. Diabetes 42: 801–813, 1993

    Article  PubMed  CAS  Google Scholar 

  7. King GL, Ishii H, Koya D: Diabetic vascular dysfunctions: A model of excessive activation of protein kinase C. Kidney Int 52: S77–S85, 1997

    Google Scholar 

  8. Derubertis FR and Craven PA: Activation of protein kinase C in glomerular cells in diabetes. Mechanisms and potential link to the pathogenesis of diabetic glomerulopathy. Diabetes 43: 1–8, 1994

    Article  PubMed  CAS  Google Scholar 

  9. Sharma K and Ziyadeh FN: Hyperglycemia and diabetic kidney disease. The case for transforming growth factor-b as a key modulator. Diabetes 44: 1139–1146, 1995

    Article  PubMed  CAS  Google Scholar 

  10. Baynes JW: Role of oxidative stress in development of complications in diabetes. Diabetes 40: 405, 1991

    Article  PubMed  CAS  Google Scholar 

  11. Nishizuka Y: Protein kinase C and lipid signaling for sustained cellular responses. FASEB 9: 484–496, 1995

    CAS  Google Scholar 

  12. Liscovitch M and Cantley LC: Lipid second messengers. Cell 77: 329–334, 1994

    Article  PubMed  CAS  Google Scholar 

  13. Nakanishi H, Brewer KA, Exton JH: Activation of the zeta isozyme of protein kinase C by phosphatidyl inositol 3, 4, 5-trisphosphate. J Biol Chem 268: 13–16, 1993

    PubMed  CAS  Google Scholar 

  14. Chang EY, Szallasi Z, Acs P, Raizada V, Wolfe PC, Fewtrell C, Blumberg PM, Rivera J: Functional effects of overexpression of protein kinase C-alpha,-beta,-delta,-epsilon, and-eta in the mast cell line RBL-2H3. J Immunol 159: 2624–2632, 1997

    PubMed  CAS  Google Scholar 

  15. Shiba T, Inoguchi T, Sportsman JR, Heath W, Bursell S, King GL: Correlation of diacylglycerol and protein kinase C activity in rat retina to retinal circulation. Am J Physiol 265: E783–E793, 1993

    PubMed  CAS  Google Scholar 

  16. Inoguchi T, Battan R, Handler E, Sportsman JR, Heath W, King GL: Preferential elevation of protein kinase C isoform II and diacylglycerol levels in the aorta and heart of diabetic rats: differential reversibility to glycemic control by islet cell transplantation. Proc Natl Acad Sci USA 89: 11059–11063, 1992

    Article  PubMed  CAS  Google Scholar 

  17. Craven PA, Davidson CM, DeRubertis FR: Increase in diacylglycerol mass in isolated glomeruli by glucose from de novo synthesis of glycerolipids. Diabetes 39: 667–674, 1990

    Article  PubMed  CAS  Google Scholar 

  18. Ishii H, Jirousek MR, Koya D, Takagi C, Xia P, Clermont A, Bursell S-E, Kern TS, Ballas LM, Heath WF, Stramm LE, Feener EP, King GL: Amelioration of vascular dysfunctions in diabetic rats by an oral PKC (3 inhibitor. Science 272: 728–731, 1996

    Article  PubMed  CAS  Google Scholar 

  19. Considine RV, Nyce MR, Allen LE, Morales LM, Triester S, Serrano J, Colberg J, Lanza-Jacoby S, Caro JF: Protein kinase C is increased in the liver of humans and rats with non-insulin-dependent diabetes mellitus: an alteration not due to hyperglycemia. J Clin Invest 95: 2938–2944, 1995

    Article  PubMed  CAS  Google Scholar 

  20. Saha AK, Kurowski TG, Colca JR, Ruderman NB: Lipid abnormalities in tissues of the KKAy mouse: effects of pioglitazone on malonyl-CoA and diacylglycerol. Am J Physiol 267: E95–E101, 1994

    PubMed  CAS  Google Scholar 

  21. 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 43: 1122–1129, 1994

    Article  PubMed  CAS  Google Scholar 

  22. Craven PA, DeRubertis FR: Protein kinase C is activated in glomeruli from streptozotocin diabetic rats. J Clin Invest 83: 1667–1675, 1989

    Article  PubMed  CAS  Google Scholar 

  23. Yasanare K, Kahno M, Kano H, Yokokawa K, Horio T, Yoshikawa J: Possible involvement of phospholipase and protein kinase C in vascular growth induced by elevated glucose concentration. Hypertension 28: 159–168. 1996

    Article  Google Scholar 

  24. Inoguchi T, Pu X, Kunisaki M, Higashi S, Feener EP, King GL: Insulin’s effect on protein kinase C and diacylglycerol induced by diabetes and glucose in vascular tissues. Am J Physiol 267: E369–E379, 1994

    PubMed  CAS  Google Scholar 

  25. Dunlop ME, Larkins RG: Pancreatic islets synthesize phospholipids de novo from glucose via acyl-dihydroxyacetone phosphate. Biochem Biophys Res Commun 132: 467–473, 1985

    Article  PubMed  CAS  Google Scholar 

  26. Ido Y, McHowat J, Chang KC, Arrogori-martelli E, Orfaliam Z, Kilo C, Corr PB, Williamson JR: Neural dysfunction and metabolic imbalances in diabetic rats. Prevention by acetyl-L carritine. Diabetes 43: 1469–1477, 1994.

    Article  PubMed  CAS  Google Scholar 

  27. Ayo SH, Radnik R, Garoni J A, Troyer DA, Kreisberg JI: High glucose increases diacylglycerol mass and activates protein kinase C in mesangial cell cultures. Am J Physiol 261: F571–F577, 1991

    PubMed  CAS  Google Scholar 

  28. Kunisaki M, Bursell S-E, Umeda F, Nawata H, King GL: Normalization of diacylglycerol-protein kinase C activation by vitamin E in aorta of diabetic rats and cultured rat smooth muscle cells exposed to elevated glucose levels. Diabetes 43: 1372–1377, 1994

    Article  PubMed  CAS  Google Scholar 

  29. Koya D, Jirousek MR, Lin Y-W, Ishii H, Kuboki K, King GL: Characteristics of protein kinase C isoform activation on the gene expression of transforming growth factor, extracellular matrix components and prostanoids in the glomeruli of diabetic rats.. J Clin Invest 100: 115–126, 1997

    Article  PubMed  CAS  Google Scholar 

  30. Kikkawa R, Haneda M, Uzu T, Koya D, Sugimoto T, Shigeta Y: Translocation of protein kinase a and ζ, in rat glomerular mesangial cells cultured under high glucose conditions. Diabetologia 37: 838–841, 1994

    Article  PubMed  CAS  Google Scholar 

  31. King GL, Shiba T, Oliver J, Inoguchi T, Bursell S-E: Cellular and molecular abnormalities in the vascular endothelium of diabetes mellitus. Annu Rev Med 45: 179–188, 1994

    Article  PubMed  CAS  Google Scholar 

  32. Winegrad AI: Does a common mechanism induce the diverse complications of diabetes? Diabetes 36: 396–406, 1987

    PubMed  CAS  Google Scholar 

  33. Xia P, Kramer RM, King GL: Identification of the mechanism for the inhibition of Na+, K+-adenosine triphosphatase by hyperglycemia involving activation of protein kinase C and cytosolic phospholipase A2. J Clin Invest 96: 733–740, 1995

    Article  PubMed  CAS  Google Scholar 

  34. Williamson JR, Kilo C: Extracellular matrix changes in diabetes mellitus. In: Scarpelli DG, Migahi G (eds) Comparative pathobiology of major age-related diseases. Liss. New York, pp 269–288, 1984

    Google Scholar 

  35. Lu TT, Yan LG, Madri JA: Integrin engagement mediates tyrosine dephosphorylation on platelet-endothelial cell adhesion molecule 1. Proc Natl Acad Sci 93: 11808–11813, 1996

    Article  PubMed  CAS  Google Scholar 

  36. Bruneval P, Foidart JM, Nochy D, Camilleri JP, Bariety J: Glomerular matrix proteins in nodular glomerulosclerosis in association with light chain deposition disease and diabetes mellitus. Hum Pathol 16: 477–484, 1985

    Article  PubMed  CAS  Google Scholar 

  37. Studer RK, Craven PA, DeRubertis FR: Role for protein kinase C in the mediation of increased fibronectin accumulation by mesangial cells grown in high-glucose medium. Diabetes 42: 118–126, 1993

    Article  PubMed  CAS  Google Scholar 

  38. Ayo SH, Radnik RA, Glass II WF, Garoni JA, Rampt ER, Appling DR, Kreisberg JI: Increased extracellular matrix synthesis and mRNA in mesangial cells grown in high-glucose medium. Am J Physiol 260: F185–F19l, 1991

    PubMed  CAS  Google Scholar 

  39. Haneda M, Kikkawa R, Horide N, Togawa M, Koya D, Kajiwara N, Ooshima A, Shigeta Y: Glucose enhances type IV collagen production in cultured rat glomerular mesangial cells. Diabetologia 34: 198–200, 1991

    Article  PubMed  CAS  Google Scholar 

  40. Fumo P, Kuncio GS, Ziyadeh FN: PKC and high glucose stimulate collagen α1(IV) transcriptional activity in a reporter mesangial cell line. Am J Physiol 267: F632–F638, 1994

    PubMed  CAS  Google Scholar 

  41. Nakamura T, Miller D, Ruoslahti E, Border WA: Production of extracellular matrix by glomerular epithelial cells in regulated by transforming growth factor-β1. Kidney Int 41: 1213–1221, 1992

    Article  PubMed  CAS  Google Scholar 

  42. Yamamoto T, Nakamura T, Noble NA, Ruoslahti E, Border WA: Expression of transforming growth factor p is elevated in human and experimental diabetic nephropathy. Proc Natl Acad Sci USA 90: 1814–1818, 1993

    Article  PubMed  CAS  Google Scholar 

  43. Sharma K, Ziyadeh FN: Renal hypertrophy is associated with upregulation of TGF-βl gene expression in diabetic BB rat and NOD mouse. Am J Physiol 267: F1094–F1101, 1994

    PubMed  CAS  Google Scholar 

  44. Sharma K, Jin Y, Guo J, Ziyadeh FN: Neutralization of TGF-β by anti-TGF-β antibody attenuates kidney hypertrophy and the enhanced extracellular matrix gene expression in STZ-induced diabetic mice. Diabetes 45: 522–530, 1996

    Article  PubMed  CAS  Google Scholar 

  45. Feke GT, Buzney SM, Ogasawara H, Fujio N, Goger DG, Spack NP, Gabbay KH: Retinal circulatory abnormalities in type 1 diabetes. Invest Ophthalmol Vis Sci 35: 2968–2975, 1994

    PubMed  CAS  Google Scholar 

  46. Bursell S-E, Clermont AC, Kinsley BT, Simonson DC, Aiello LM, Wolpert HA: Retinal blood flow changes in patients with insulin-dependent diabetes mellitus and no diabetic retinopathy. Invest Ophthalmol Vis Sci 37: 886–897, 1996

    PubMed  CAS  Google Scholar 

  47. Small KW, Stefansson E, Hatchell D: Retinal blood flow in normal and diabetic dogs. Invest Ophthalmol Vis Sci 28: 672–675, 1987

    PubMed  CAS  Google Scholar 

  48. Clermont AC, Brittis M, Shiba T, McGovern T, King GL, Bursell S-E: Normalization of retinal blood flow in diabetic rats with primary intervention using insulin pumps. Invest Ophthalmol Vis Sci 35: 981–990, 1994

    PubMed  CAS  Google Scholar 

  49. Miyamoto K, Ogura Y, Nishiwaki H, Matsuda N, Honda Y, Kato S, Ishida H, Seino Y: Evaluation of retinal microcirculatory alterations in the Goto-Kakizaki rat. Invest Ophthalmol Vis Sci 37: 898–905, 1996

    PubMed  CAS  Google Scholar 

  50. Kohner EM: Role of blood flow and impaired autoregulation in the pathogenesis of diabetic retinopathy. Diabetes 44: 603–607, 1995

    Article  PubMed  CAS  Google Scholar 

  51. Tesfayes S, Malik R, Ward JD: Vascular factors in diabetic neuropathy. Diabetologia 37: 847–851.

    Google Scholar 

  52. Cameron NE, Cotter MA, Lai K, Hohman TC: Effect of protein kinase C inhibition on nerve function, blood flow and Na+K+ ATPase defects in diabetic rats. Diabetes 46(supple.l): 31A–0121, 1997

    Google Scholar 

  53. Takagi C, Bursell S-E, Lin Y-W, Takagi H, Duh E, Jiang Z, Clermont AC, King GL: Regulation of retinal hemodynamics in diabetic rats by increased expression and action of endothelin-1. Invest Ophthalmol Vis Sci 37: 2504–2518, 1996

    PubMed  CAS  Google Scholar 

  54. Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, Pasquale LR, Thieme H, Iwamoto MA, Park JE, Nguyen HV, Aiello LM, Ferrara N, King GL: Vascular endothelial growth factor in ocular fluids of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 331: 1480–1487, 1994

    Article  PubMed  CAS  Google Scholar 

  55. Williams B, Gallachen B, Patel H, Orme C: Glucose-induced protein kinase C activation regulates vasular permeability factor mRNA expression and peptide production by vascular smooth muscle cells in vitro. Diabetes 46: 1497–1503, 1997.

    Article  PubMed  CAS  Google Scholar 

  56. Christiansen JS, Gammelgaard J, Frandsen M, Parving HH: Increased kidney size, glomerular filtration rate and renal plasma flow in short-term insulin-dependent diabetes. Diabetologia 20: 451–456, 1981

    PubMed  CAS  Google Scholar 

  57. Hostetter TH, Troy JL, Brenner BM: Glomerular hemodynamics in experimental diabetes mellitus. Kidney Int 19: 410–415, 1981

    Article  PubMed  CAS  Google Scholar 

  58. O’Donnell MP, Kasiske BL, Keane WF: Glomerular hemodynamic structural alterations in experimental diabeties mellitus. FASEBJ2: 2339–2347, 1988.

    Google Scholar 

  59. Anderson S, Jung FF, Ingelfinger JR: Renal renin-angiotensin system in diabetes: functional immunohistochemical and molecular biologica correlations. AM J Physiol. 265: F477–F486. 1993.

    PubMed  CAS  Google Scholar 

  60. Craven PA, Caines MA, DeRubertis FR: Sequential alterations in glomerular prostaglandin and thromboxane synthesis in diabetic rats: relationship to the hyperfiltration of early diabetes. Metabolism 36: 95–103, 1987

    Article  PubMed  CAS  Google Scholar 

  61. Williams B, Schrier RW: Glucose-induced protein kinase C activity regulates arachidonic acid release and eicosanoid production by cultured glomerular mesangial cells. J Clin Invest 92: 2889–2896, 1993

    Article  PubMed  CAS  Google Scholar 

  62. Haneda M, Arakis I, Togaro M, Sugimoto T, Isono M, Kikkawa R: Mitogen activated protein kinase C is activated in glomeruli of diabetic rats and glomerular mesangial cells cultured under high glucose conditions. Diabetes 46: 847–853, 1997.

    Article  PubMed  CAS  Google Scholar 

  63. Bank N, Aynedjian HS: Role of EDRF (nitric oxide) in diabetic renal hyperfiltration. Kidney Int 43: 1306–1312, 1993

    Article  PubMed  CAS  Google Scholar 

  64. Tolins JP, Shultz PJ, Raij L, Brown DM, Mauer SM: Abnormal renal hemodynamic response to reduced renal perfusion pressure in diabetic rats: role of NO. Am J Physiol 265: F886–F895, 1993

    PubMed  CAS  Google Scholar 

  65. Sharma K, Danoff TM, DePiero A, Ziyadeh FN: Enhanced expression of inducible nitric oxide synthase in murine macrophages and glomerular mesangial cells by elevated glucose levels: possible mediation via protein kinase C. Biochem Biophys Res Commun 207: 80–88, 1995

    Article  PubMed  CAS  Google Scholar 

  66. Graier WF, Simecek S, Kukovetz WR, Kostner GM: High D-glucose-induced changes in endothelial Ca2+/EDRF signaling are due to generation of superoxide anions. Diabetes 45(10): 1386–1395, 1996

    Article  PubMed  CAS  Google Scholar 

  67. Muniyappa R, Srinivas PR, Ram JL, Walsh MF, Sowers JR: Calcium and protein kinase C mediate high-glucose-induced inhibition of inducible nitric oxide synthase in vascular smooth muscle cells. Hypertension 31(1 PT 2): 289–295, 1998

    Article  PubMed  CAS  Google Scholar 

  68. Nishio E, Watanabe Y: Glucose-induced down-regulation of NO production and inducible NOS expression in cultured rat aortic vascular smooth muscle cells: role of protein kinase C. Biochem Biophys Res Commun 229(3): 857–863, 1996

    Article  PubMed  CAS  Google Scholar 

  69. McVeigh GE, Brennan GM, Johnston GD, McDermott BJ, McGrath LT, Henry WR, Andrews JW: Impaired endothelium-dependent and independent vasodilation in patients with Type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 35: 771–776, 1992

    PubMed  CAS  Google Scholar 

  70. Tesfamariam B, Brown ML, Cohen RA: Elevated glucose impairs endothelium-dependent relaxation by activating protein kinase C. J Clin Invest 87: 1643–1648, 1991

    Article  PubMed  CAS  Google Scholar 

  71. Williamson JR, Chang K, Tilton RG, Prater C, Jeffrey JR, Weigel C, Sherman WR, Eades DM, Kilo C: Increased Vascular permeability in spontaneously diabetic BB/W rats and in rats with mild versus severe streptozocin-induced diabetes. Diabetes 36: 813–821, 1987

    Article  PubMed  CAS  Google Scholar 

  72. Lynch JJ, Ferro TJ, Blumenstock FA, Brockenauer AM, Malik AM: Increased endothelial albumin permeability mediated by protein kinase C activation. J Clin Invest 85: 1991–1998, 1990

    Article  PubMed  CAS  Google Scholar 

  73. Werth DK, Niedel JE, Pastan I: Vinculin, a cytoskeletal substrate of protein kinase C. J Biol Chem 258: 11423–11426, 1983

    PubMed  CAS  Google Scholar 

  74. Stasek JE, Patterson CE, Garcia JGN: Protein kinase C phosphorylates caldesmon77 and vimentin and enhances albumin permeability across cultured bovine pulmonary artery endothelial cell monolayers. J Cell Physiol 153: 62–75, 1992

    Article  PubMed  Google Scholar 

  75. Nagpala PG, Malik AB, Vuong PT, Lum H: Protein kinase C β1, overexpression augments phorbol ester-induced increase in endothelial permeability. J Cell Physiol 166: 249–255, 1996

    Article  PubMed  CAS  Google Scholar 

  76. Xia P, Aiello LP, Ishii H, Jiang Z, Park DJ, Robinson GS, Takagi H, Newsome WP, Jirousek MR, King GL: Characterization of vascular endothelial growth factor’s effect on the activation of protein kinase C, its isoforms, and endothelial cell growth. J Clin Invest 98: 2018–2026, 1996

    Article  PubMed  CAS  Google Scholar 

  77. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD: The effect of angiotensin converting enzyme inhibitor on diabetic nephropathy. N Engl J Med 329: 1456–1462, 1993

    Article  PubMed  CAS  Google Scholar 

  78. Kunisaki M, Bursell S-E, Clermont AC, Ishii H, Ballas LM, Jirousek MR, Umeda F, Nawata H, King GL: Vitamin E prevents diabetes-induced abnormal retinal blood flow via the diacylglycerol-protein kinase C pathway. Am J Physiol 269: E239–E246, 1995

    PubMed  CAS  Google Scholar 

  79. Tasinato A, Boscoboinik D, Bartoli GM, Maroni P, Azzi A: d--tocopherol inhibition of vascular smooth muscle cell proliferation occurs at physiological concentrations, correlates with protein kinase C inhibition and is independent of its antioxidant properties. Proc. Natl. Acad. Sci. USA 92: 12190–12194, 1995

    Article  PubMed  CAS  Google Scholar 

  80. Koya D, Lee I-K, Ishii H, Kanoh H, King GL: Prevention of glomerular dysfunctions in diabetic rats by treatment of d--tocopherol. J Am Soc Nephrol 1997

    Google Scholar 

  81. Konishi H, Tanaka M, Takemura Y, Matsuzaki H, Ono Y, Kikkawa U, Nishizuka Y: Activation of protein kinase C by tyrosine phosphorylation in response to H202. Proc. Natl. Acad. Sci. USA 94: 11233–11237, 1997

    Article  PubMed  CAS  Google Scholar 

  82. Wakasaki H, Koya D, Schuen FJ, Jirousek MR, Ways DK, Hoit BD, Walsh RA, King GL: Targeted overexpression of protein kinase C isoform in myocardium causes cardiomyopathy. Proc Natl Acad Sci USA 94: 9320–9325, 1997

    Article  PubMed  CAS  Google Scholar 

  83. Porte D Jr., Schwartz MW: Diabetes complications: why is glucose potentially toxic? Science 272: 699–700, 1996

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. George L. King M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. DVA Medical Center and University of California, Irvine, USA

    Ellis R. Levin M.D.

  2. City of Hope Medical Center, Duarte, California, USA

    Jerry L. Nadler M.D.

Rights and permissions

Reprints and permissions

Copyright information

© 1998 Springer Science+Business Media New York

About this chapter

Cite this chapter

King, G.L. (1998). The Role of Protein Kinase C Activation in the Development of Diabetic Vascular Complications. In: Levin, E.R., Nadler, J.L. (eds) Endocrinology of Cardiovascular Function. Endocrine Updates, vol 1. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5569-8_10

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-5569-8_10

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7547-0

  • Online ISBN: 978-1-4615-5569-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation