Journal Mobile Options
Table of Contents
Vol. 53, No. 2, 2000
Issue release date: 2000

Role of Growth Factors in the Development of Diabetic Complications

Chiarelli F. · Santilli F. · Mohn A.
To view the fulltext, log in and/or choose pay-per-view option

Individual Users: Register with Karger Login Information

Please create your User ID & Password





Contact Information











I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in

Abstract

The structural changes characterising diabetic microangiopathy, which may be referred to as ’abnormal growth’ and ’impaired regeneration’, strongly suggest a role for a number of aberrantly expressed growth factors, possibly acting in combination, in the development of these complications. This initial speculation has been supported by the detection of increased concentrations of several growth factors in the target tissues of diabetic long-term complications, and by enhanced expression of these growth factors consequent to the activation of the biochemical pathways linking hyperglycaemia to microvascular changes: the polyol pathway; non-enzymatic glycation of proteins; vasoactive hormones; oxidative stress, and hyperglycaemic pseudohypoxia. As to nephropathy, insulin-like growth factor I (IGF-I) seems to be implicated in the earlier stages of the disease, while transforming growth factor β (TGFβ) is involved both in the early and later stages, being responsible, at least in part, for extracellular matrix (ECM) accumulation. Vascular endothelial growth factor (VEGF) plays a pivotal role both in non-proliferative and proliferative retinopathy. Finally, deficiency of several neurotrophic factors, namely nerve growth factor (NGF) and IGF-I has been related to the degeneration or impaired regeneration occurring in diabetic neuropathy. Knowledge of the involvement of growth factors in diabetic microangiopathy opens the way to new therapeutic interventions aimed at blocking the deleterious actions of several growth factors.

Copyright © 2000 S. Karger AG, Basel



Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Abboud H: Growth factors and diabetic nephropathy: An overview. Kidney Int 1997;52 (suppl 60):3–6.
  2. Nakamura T, Fukui M, Ebihara I, Osada S, Nagaoka I, Tomino Y, Koide H: mRNA expression of growth factors in glomeruli from diabetic rats. Diabetes 1993;42:450–456.
  3. DCCT Study Group: The Diabetes Control and Complications Trial Research Group: The effect of intensive treatment of diabetes on the development of long-term complications in insulin dependent diabetes mellitus. N Engl J Med 1993;329:977–986.
  4. Aiello LP, Bursell SE, Clermont A, Duh E, Ishii E, Takagi C, Mori F, Ciulla TA, Ways K, Jirousek M, Smith LEH, King GL: Vascular endothelial growth factor-induced retinal permeability is mediated by protein kinase C in vivo and suppressed by an orally effective β-isoform-selective inhibitor. Diabetes 1997;46:1473–1480.
  5. Kim SJ, Glick A-B, Sporn MB, Roberts AB: Characterization of the promoter region of the human transforming growth factor-beta gene. J Biol Chem 1989;264:402–404.
  6. Craven PA, Studer RK, Negrete H, DeRubertis FR: Protein kinase C in diabetic nephropathy. J Diabetes Complications 1995;9:241–245.

    External Resources

  7. Murata T, Nagai R, Ishibashi T, Inomata H, Ikeda K, Horiushi S: The relationship between the accumulation of advanced glycation end products and expression of vascular endothelial growth factor in human diabetic retinas. Diabetologia 1997;40:764–769.
  8. Kagami S, Border WA, Miller DE, Noble NA: Angiotensin II stimulates extracellular matrix protein synthesis through induction of transforming growth factor-β in rat glomerular mesangial cells. J Clin Invest 1994;93:2431–2437.
  9. Fukui M, Nakamura T, Ebihara I, Makita Y, Osada S, Tomino Y, Koide H: Effects of enalapril on endothelin-1 and growth factor gene expression in diabetic rat glomeruli. J Lab Clin Med 1994;123:763–768.
  10. Young BA, Johnson RJ, Alpers CE, Eng E, Gordon K, Floege J: Cellular events in the evolution of experimental diabetic nephropathy. Kidney Int 1995;47:935–944.
  11. Fogo A, Ichikawa I: Evidence for the central role of glomerular growth promoters in the development of sclerosis. Semin Nephrol 1989;9:329–342.

    External Resources

  12. Wolf G: Molecular mechanisms of angiotensin II in the kidney: Emerging role in the progression of renal disease beyond haemodynamics. Nephrol Dial Transplant 1998;13:1131–1142.
  13. Yamamoto T, Nakamura T, Noble NA, Ruoshlati E, Border WA: Expression of transforming growth factor β is elevated in human and experimental diabetic nephropathy. Proc Natl Acad Sci USA 1993;90:1814–1818.
  14. Abboud HE: Growth factors in glomerulonephritis. Kidney Int 1993;43:252–267.
  15. Flyvbjerg A, Landau D, Domene H, Hernandez L, Gronbaek H, Leroith D: The role of growth hormone, insulin-like growth factors (IGFs) and IGF-binding proteins in experimental diabetic kidney disease. Metabolism 1995;44:67–71.
  16. Bach LA, Jerums G: Effect of puberty on the initial kidney growth and rise in kidney IGF-I in diabetic rats. Diabetes 1990;39:557–562.
  17. Clayton KL, Holly JM, Carlsson LM, Jones J, Cheetham TD, Taylor AM, Dunger DB: Loss of the normal relationships between growth hormone, growth hormone binding protein and insulin-like growth factor I in adolescents with insulin-dependent diabetes mellitus. Clin Endocrinol 1999;41:517–524.
  18. Bach LA, Cox AJ, Mendelsohn FAO, Herington AC, Werther GA, Jerums G: Focal induction of IGF binding proteins in proximal tubules of diabetic rat kidney. Diabetes 1992;41:499–507.
  19. Landau D, Chin E, Bondy C, Domene H, Roberts CT, Gronbaek H, Flyvbjerg A, Leroith D: Expression of insulin-like growth factor binding proteins in the rat kidney: Effects of long term diabetes. Endocrinology 1995;136:1835–1842.
  20. De Vroede MA, Tseng LY, Katsoyannis PG, Nissley SP, Rechler MM: Modulation of insulin-like growth factor I binding to human fibroblast monolayer cultures by insulin-like growth factors carrier proteins released to the incubation media. J Clin Invest 1986;77:602–613.
  21. Horney M, Shirley DW, Kurtz DT, Rosenzweig SA: Elevated glucose increases mesangial cell sensitivity to insulin-like growth factor I. Am J Physiol 1998;274:F1045–F1053.

    External Resources

  22. Flyvbjerg A, Frystyk J, Osterby R, Orskov H: Kidney IGF-I and renal hypertrophy in GH-deficient diabetic dwarf rats. Am J Physiol 1992;262:E956–E962.

    External Resources

  23. Guler HP, Schimid C, Zapf J, Froesch ER: Effects of insulin-like growth factor I in man. Acta Paediatr Scand Suppl 1990;367:52–54.
  24. Guler HP, Schimid C, Zapf J, Froesch ER: Effects of recombinant insulin-like growth factor I on insulin secretion and renal function in normal human subjects. Proc Natl Acad Sci USA 1989;86:2868–2872.
  25. Hirschberg R, Kopple JD, Blantz RC, Tucher BJ: Effects of recombinant human insulin-like growth factor I on glomerular dynamics in the rat. J Clin Invest 1991;87:1200–1206.
  26. Hirschberg R, Kopple JD: Evidence that IGF-I increases renal plasma flow and glomerular filtration rate in fasted rats. J Clin Invest 1989;83:326–330.
  27. Cummings E, Sochett E, Dekker MG, Lawson ML, Daneman D: Contribution of growth hormone and IGF-I to early diabetic nephropathy in type I diabetes. Diabetes 1998;47:1341–1346.
  28. Hanaire-Broutin H, Sallerin-Caute B, Poncet ME, Tauber M, Bastide R, Chale JJ, Rosenfeld S: Effects of intraperitoneal insulin delivery on growth hormone binding protein, insulin-like growth factor (IGF-1), and IGF-binding protein 3 in IDDM. Diabetologia 1996;39:1498–1504.
  29. Ziyadeh FN, Sharma K: Role of transforming growth factor beta in diabetic glomerulosclerosis and renal hypertrophy. Kidney Int 1995;48(suppl 51):34–36.
  30. Yokoyama H, Deckert T: Central role of TGF-β in the pathogenesis of diabetic nephropathy and macrovascular complications: A hypothesis. Diabet Med 1996;13:313–320.
  31. Wolf G, Sharma K, Chen Y, Ericksen M, Ziyadeh FN: High glucose induced proliferation in mesangial cells is reversed by autocrine TGF-β. Kidney Int 1992;42:647–656.
  32. Wolf G, Schroeder R, Ziyadeh FN, Thaiss F, Zahner G, Stahl RAH: High glucose stimulates expression of p27 in cultured mouse mesangial cells: Relationship with hypertrophy. Am J Physiol 1997;273:348–356.
  33. Kuan CJ, Al-Douahji M, Shankland SJ: The cyclin kinase inhibitor p21 is increased in experimental diabetic nephropathy: Potential role in glomerular hypertrophy. J Am Soc Nephrol 1998;9:986–1003.
  34. Van der Born J, Berden JHM: Selective proteinuria in diabetic nephropathy in the rat is associated with a relative decrease in glomerular basement membranes. Diabetologia 1995;38:161–172.
  35. Shankland SJ, Scholey JW: Expression of transforming growth factor β1 during diabetic renal hypertrophy. Kidney Int 1994;42:430–442.
  36. Oh JH, Ha H, Yu MR, Lee HB: Sequential effects of high glucose on mesangial cell transforming growth factor-β1 and fibronectin synthesis. Kidney Int 1998;54:1872–1878.
  37. Iwano M, Kubo A, Nishino T, Sato H, Nishioka H, Akai Y, Kurioka H, Fujii Y, Kanauchi M, Shiiki H, Dohi K: Quantification of glomerular TGF-β1 mRNA in patients with diabetes mellitus. Kidney Int 1996;49:1120–1126.
  38. Park IS, Kiyomoto H, Abboud HE, Abboud S: Expression of transforming growth factor β and type IV collagen in early streptozotocin-induced diabetes. Diabetes 1997;46:473–480.
  39. Singh R, Alavi N, Singh AK, Leehey DJ: Role of angiotensin II in glucose-induced inhibition of mesangial matrix degradation. Diabetes 1999;48:2066–2073.
  40. Schmidt AM, Hori O, Brett J, Yan DS, Wautier JL, Stern D: Cellular receptors for advanced glycation end products. Implication for induction of oxidant stress and cellular dysfunction in the pathogenesis of vascular lesions. Arterioscler Thromb 1994;14:1521–1528.

    External Resources

  41. Beisswenger PJ, Moore LL, Brinck-Johnsen T, Curphey TJ: Increased collagen-linked pentosidine levels and advanced glycosylation end-products in early diabetic nephropathy. J Clin Invest 1993;92:212–217.
  42. Ziyadeh FN, Han DC, Cohen JA, Guo J, Cohen MP: Glycated albumin stimulates fibronectin gene expression in glomerular mesangial cells: Involvement of the growth factor-β system. Kidney Int 1998;53:631–638.
  43. Kim SJ, Angel P, Lafyatis R, Hattori K, Kim KI, Sporn MB, Karin M, Roberts AB: Autoinduction of transforming growth factor-beta 1 is mediated by the AP-1 complex. Mol Cell Biol 1990;10:1492–1497.
  44. Kim SJ, Jeang KT, Glick A-B, Sporn MB, Roberts AB: Promoter sequences of the human transforming growth factor-beta 1 gene responsive to transforming growth factor-beta 1 autoinduction. J Biol Chem 1989;264:7041–7045.
  45. Ingram AJ, Ly H, Thai K, Kang M, Scholey JW: Activation of mesangial cell signaling cascades in response to mechanical strain. Kidney Int 1999;55:476–485.
  46. Tamsma JT, van den Born J, Bruijin J-A: Expression of glomerular extracellular matrix components in human diabetic nephropathy: Decrease of heparane sulphate in the glomerular basement membrane. Diabetologia 1994;37:313–320.
  47. Jakeman LB, Winer JW, Bennet GL, Altar CA, Ferrara N: Binding sites for vascular endothelial growth factor are localized on endothelial cells in adult rat tissues. J Clin Invest 1992;89:244–253.
  48. Simon M, Rockl W, Hornig G, Grone EF, Theis H, Weich HA, Fuchs E, Yayon A, Grone HJ: Expression of VEGF/VPF in fetal and adult human kidney: Localization and VEGF binding sites. J Am Soc Nephrol 1998;9:1032–1044.
  49. Williams B: A potential role for angiotensin II-induced vascular endothelial growth factor expression in the pathogenesis of diabetic nephropathy? Miner Electrolyte Metab 1998;24:400–405.
  50. Simon M, Johren O, Kullmer J, Plate KH, Risau W, Fuchs E: Expression of vascular endothelial growth factor and its receptors in human renal ontogenesis and in adult kidney. J Am Soc Nephrol 1995;268:F240–F250.
  51. Pupilli C, Lasagni L, Romagnani P, Bellini F, Mannelli M, Misciglia N, Mavilia C, Vellei U, Villari D, Serio M: Angiotensin II stimulates the synthesis and secretion of vascular permeability factor/vascular endothelial growth factor in human mesangial cells. J Am Soc Nephrol 1999;10:245–255.
  52. Inaba T, Ishibashi T, Gotoda T, Kawamura M, Morino N, Nojima Y, Kawakami M, Yazaki Y, Yamada N: Enhanced expression of platelet-derived growth factor-β receptor by high glucose. Involvement of platelet-derived growth factor in diabetic angiopathy. Diabetes 1996;45:507–512.
  53. Sivalingham A, Kenney J, Benson W: Basic fibroblast growth factor levels in the vitreous of patients with proliferative diabetic retinopathy. Arch Ophthalmol 1999;108:869–872.
  54. Fredj-Reggrobelet D, Baudouin C, Negre F: Acidic fibroblast growth factor and other growth factors in preretinal membranes from patients with diabetic retinopathy and proliferative vitreoretinopathy. Ophthalmic Res 1991;23:154–161.
  55. Morishita R, Nakamura S, Nakamura Y: Potential role of an endothelium-specific growth factor, hepatocyte growth factor, on endothelial damage in diabetes. Diabetes 1997;46:138–142.
  56. Armstrong D, Augustin AJ, Spengler R: Detection of vascular endothelial growth factor and tumor necrosis factor alpha in epiretinal membranes of proliferative diabetic retinopathy, proliferative vitreoretinopathy and macular pucker. Ophthalmologica 1998;212:410–412.
  57. Katsura Y, Okano T, Noritake M, Kosano H, Nishigori H, Kado S, Matsuoka T: Hepatocyte growth factor in vitreous fluid of patients with proliferative diabetic retinopathy and other retinal disorders. Diabetes Care 1998;21:1759–1763.
  58. Nishimura M, Nakano K, Ushiyama M: Increased serum concentration of human hepatocyte growth factor in proliferative diabetic retinopathy. J Clin Endocrinol Metab 1998;83:195–198.
  59. Ambati J, Chalam KV, Chawla DK: Elevated gamma-aminobutyric acid, glutamate, and vascular endothelial growth factor levels in the vitrous of patients with proliferative diabetic retinopathy. Arch Ophthalmol 1997;115:1161–1166.
  60. Meyer-Schwickerath R, Pfeiffer A, Blum WF, Freyberger H, Klein M, Losche C, Rollmann R, Schatz H: Vitreous levels of the insulin-like growth factor I and II, and the insulin-like growth factor binding proteins 2 and 3, increase in neovascular eye disease: Studies in nondiabetic and diabetic subjects. J Clin Invest 1993;92:2620–2625.
  61. Vinores SA, Henderer JD, Mahlow J, Chiu C, Derevjanik NL, Larochelle W: Isoforms of platelet-derived growth factor and its receptors in epiretinal membranes: Immunolocalization to retinal pigmented epithelial cells. Exp Eye Res 1995;60:607–619.
  62. Patel B, Hiscott P, Charteris D, Mather J, McLeod DS, Boulton M: Retinal and preretinal localisation of epidermal growth factor, transforming growth factor alpha, and their receptor in proliferative diabetic retinopathy. Br J Ophthalmol 1994;78:714–718.
  63. Khaliq A, Patel B, Jarvis-Evans J, Moriarty P, McLeod DS, Boulton M: Oxygen modulates production of bFGF by retinal cells in vitro. Exp Eye Res 1999;60:415–424.
  64. Arnold D, Moshayedi P, Schoen T, Lomas B, Chader G, Waldbillig R: Distribution of IGF-I and -II binding proteins (IGFBPs) and IGFBP mRNA in ocular fluids and tissues: Potential sites of synthesis in aqueous and vitreous. Exp Eye Res 1993;56:555–565.
  65. Danias J, Stylianopoulou F: Expression of IGF-I and IGF-II in the adult rat eye. Curr Eye 1990;9:379–386.
  66. Malecaze F, Clamens F, Simorre-Pinatel V, Mathis A, Cholet P, Favard C: Detection of vascular endothelial growth factor messenger mRNA and vascular endothelial growth factor activity in proliferative diabetic retinopathy. Arch Ophthalmol 1994;112:1476–1482.
  67. Boulton M, Patel B, Khaliq A, Moriarty P, Jarvis-Evans J, McLeod DS: Modulators and milieu in preretinal neovascularization. Eye 1992;6:560–565.

    External Resources

  68. Singh A, Boulton M, Lane C, Forrester J, Gaal J, McLeod DS: Inhibition of microvascular endothelial cell proliferation by vitreous following retinal scatter photocoagulation. Br J Ophthalmol 1990;74:328–332.
  69. Clemmons D: IGF-binding proteins and their functions. Mol Reprod Dev 1993;35:368–375.

    External Resources

  70. Hanneken A, Baird A: Soluble forms of the high affinity fibroblast growth factor receptor in human vitreous fluid. Invest Ophthalmol Vis Sci 1995;36:1192–1196.
  71. Merimee TJ: Diabetic retinopathy. N Engl J Med 1999;322:978–982.
  72. Hyer SL, Sharp PS, Burrin JM, Kohner EM: Progression of diabetic retinopathy and changes in serum insulin-like growth factor I (IGF-I) during continuous subcutaneous insulin infusion. Horm Metab Res 1989;21:18–22.

    External Resources

  73. Stoker M, Gherardi E, Perryman M, Gray J: Scatter factor is a fibroblast-derived modulator of epithelial cell. Nature 1987;327:239–242.
  74. Stavri GT, Zachari IC, Baskerville PA, Martin JF, Erusalimsky JD: Basic fibroblast growth factor upregulates the expression of vascular endothelial growth factor in vascular smooth muscle cells: Synergistic interaction with hypoxia. Circulation 1995;92:11–14.
  75. Williams B: Vascular permeability/vascular endothelial growth factors: A potential role in the pathogenesis and treatment of vascular disease. Vasc Med 1996;1:251–258.
  76. Aiello LP, Avery R, Arrig P: Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 1994;331:1480–1487.
  77. Ferrara N: Role of vascular endothelial growth factor in the regulation of angiogenesis. Kidney Int 1999;56:794–814.
  78. Aiello L: Hypoxic regulation of vascular endothelial growth factor in retinal cells. Arch Ophthalmol 1995;113:1538–1544.
  79. Yang Q, Zwijsen A, Slegers H: Purification and characterization of VEGF/VPF secreted by human retinal pigment epithelial cells. Endothelium 1994;2:73–85.
  80. Thieme H, Aiello LP, Takagi H: Comparative analysis of vascular endothelial growth factor (VEGF) receptors on retinal and aortic microvascular endothelial cells. Diabetes 1994;44:98–103.
  81. Takagi H, King GL, Aiello LP: Identification and characterization of vascular endothelial growth factor receptor (Flt) in bovine retinal pericyte. Diabetes 1996;45:1016–1023.
  82. Williams B, Quinn-Baker A, Gallacher B, Lodwig D: Angiotensin II increases vascular permeability factor gene expression by human vascular smooth muscle cells. Hypertension 1995;25:913–917.
  83. Williams B, Gallacher B, Patel H, Orme C: The potential role role of vasopressin as a modulator of endothelial function; in Saito T, Kurokawa K, Yoshida S (eds): Neurohypophysis: Recent Progress of Vasopressin and Oxytocin Research. Amsterdam, Elsevier, 1995, pp 573–582.
  84. Brogi E, Wu T, Namiki A, Isner JM: Indirect angiogenic cytokines upregulate VEGF and bFGF gene expression in vascular smooth muscle cells, whereas hypoxia upregulates VEGF expression only. Circulation 1994;90:649–652.
  85. Shweiki D, Itin A, Soffer D, Keshet E: Vascular endothelial growth factor induced by hypoxia may mediate hypoxia initiated angiogenesis. Nature 1992;359:843–845.
  86. Aiello LM, Cavallerano J D: Ocular complications of diabetes mellitus; in Kahn CR, Weir GC (eds): Joslin’s Diabetes mellitus, ed 13. Philadelphia, Lea & Febiger, 1994, pp 771–793.
  87. Amin RH, Frank RN, Kennedy A: Vascular endothelial growth factor is present in glial cells of the retina and optic nerve of human subjects with nonproliferative diabetic retinopathy. Invest Ophthalmol Vis Sci 1997;38:36–47.
  88. Lutty GA, McLeod DS, Merges C: Localization of vascular endothelial growth factor in human retina and choroid. Arch Ophthalmol 1996;114:971–977.
  89. Sone H, Kawakami Y, Okuda Y, Sekine Y, Honmura S, Matsuo K, Segawa T, Suzuki H, Yamashita K: Ocular vascular endothelial growth factor levels in diabetic rats are elevated before observable retinal proliferative changes. Diabetologia 1997;40:726–730.
  90. Tolentino MJ, Miller JW, Gragoudas ES: Intravitreous injections of vascular endothelial growth factor in human retina and choroid. Ophthalmology 1996;103:1820–1828.
  91. Clermont AC, Aiello LP, Fumihico M, Aiello LM, Bursell SE: Vascular endothelial growth factor and severity of non-proliferative diabetic retinopathy mediate retinal hemodynamics in vivo: A potential role for vascular endothelial growth factors in the progression of non-proliferative diabetic retinopathy. Am J Ophthalmol 1997;124:433–446.
  92. Wolf S, Arend O, Toonen H: Measurement of retinal micro and macrocirculation in patients with diabetes mellitus with scanning laser ophthalmoscopy. Clin Vis Sci 1992;7:461–469.
  93. Ernest JT, Goldstick TK, Engerman RL: Hyperglycemia impairs retinal oxygen autoregulation in normal and diabetic dogs. Invest Ophthalmol Vis Sci 1983;24:985–989.

    External Resources

  94. Takagi C, Bursell SE, Lin YW: Regulation of retinal hemodynamics in diabetic rats by increased expression and action of endothelin-1. Invest Ophthalmol Vis Sci 1996;37:2504–2518.
  95. Kihara M, Low PA: Impaired vasoreactivity to nitric oxide in experimental diabetic neuropathy. Exp Neurol 1995;132:180–185.
  96. Smith LE, Shen W, Perruzzi C, Soker S, Kinose F, Xu X, Robinson G, Driver S, Bischoff J, Zhang B, Schaeffer JM, Senger DR: Regulation of vascular endothelial growth factor-dependent retinal neovascularization by insulin-like growth factor-1 receptor. Nat Med 1999;5:1390–1395.
  97. Properzi G, Terengho G, Gu XH: Early increase precedes a depletion of endothelin-1 but not of von Willebrand factor in cutaneous microvessels of diabetic patients. J Pathol 1995;175:243–252.

    External Resources

  98. Asahara T, Murohara T, Sullivan T: Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997;275:964–967.
  99. Stern P: Diabetic nerve damage may be reversible. Am J Pathol 1999;155:1651–1660.
  100. Hellweg R, Hartung HD: Endogenous levels of nerve growth factor (NGF) are altered in experimental diabetes mellitus: A possible role for NGF in the pathogenesis of diabetic neuropathy. J Neurosci Res 1990;26:258–267.
  101. Jakobsen J, Brimijoin S, Skau K, Sidenius P, Wells D: Retrograde axonal transport of transmitter enzymes, fucose-labeled protein, and nerve growth factor in streptozotocin diabetic rats. Diabetes 1981;30:797–803.

    External Resources

  102. Robinson JP, Willars GB, Tomlison GR, Keen P: Axonal transport and tissue contents of substance P in rats with long-term streptozotocin-diabetes: Effects of the aldose reductase inhibitor ‘statil’. Brain Res 1987;426:339–348.
  103. Tomlinson DR, Robinson JP, Willars GB, Keen P: Deficient axonal transport of substance P in streptozotocin-induced diabetic rats: Effects of sorbinil and insulin. Diabetes 1988;37:488–493.

    External Resources

  104. Fernyhough P, Diemel LT, Hardy J, Brewster WJ, Mohiuddin L, Tomlinson DR: Human recombinant nerve growth factor replaces deficient neurotrophic support in the diabetic rat. Eur J Neurosci 1995;7:1107–1110.
  105. Ishii DN, Lupien S: Insulin like growth factors protect against diabetic neuropathy: Effects on sensory nerve regeneration in rats. J Neurosci Res 1995;40:138–144.
  106. Zhuang HX, Snyder CK, Ishii DN: Insulin-like growth factors reverse or arrest diabetic neuropathy: Effects on hyperalgesia and impaired nerve regeneration in rats. Exp Neurol 1996;140:198–205.
  107. Zhuang H, Wuarin L, Fei Z, Ishii DN: Insulin-like growth factor (IGF) gene expression is reduced in neural tissues and liver from rats with non-insulin-dependent diabetes mellitus, and IGF treatment ameliorates diabetic neuropathy. J Pharmacol Exp Ther 1997;283:366–374.
  108. Ebendal T: Function and evolution in the NGF family and its receptors. J Neurosci Res 1992;32:461–470.

    External Resources

  109. Levi-Montalcini R, Calissano P: Nerve growth factor as a paradigm for other polypeptide growth factors. Trends Neurosci 1999;9:473–477.
  110. Thoenen H, Bandtlow C, Heumann R: The physiological function of nerve growth factor in the central nervous system: Comparison with the periphery. Rev Physiol Biochem Pharmacol 1987;109:146–178.
  111. Scarpini E, Ross AH, Rosen JL, Brown MJ, Rostami A, Koprowski H: Expression of nerve growth factor receptor during human peripheral nerve development. Dev Biol 1988;125:301–310.
  112. Yan Q, Johnson EN: A quantitative study of the developmental expression of nerve growth factor (NGF) receptor in rats. Dev Biol 1987;121:139–148.

    External Resources

  113. Schmidt RE: The role of nerve growth factor in the pathogenesis and therapy of diabetic neuropathy. Diabet Med 1993;10(suppl 2):10–13.
  114. Faradji V, Sotelo J: Low serum levels of nerve growth factor in diabetic neuropathy. Acta Neurol Scand 1999;81:402–406.
  115. Tomlinson DR, Fernyhough P, Diemel LT: Role of neurotrophins in diabetic neuropathy and treatment with nerve growth factors. Diabetes 1997;46(suppl 2):43–47.
  116. Anand P: Nerve growth factor in diabetic neuropathy. Lancet 1998;352:1629–1630.

    External Resources

  117. Crosby SR, Tsigos C, Anderton CD, Gordon C, Young RJ, White A: Elevated plasma insulin like growth factor binding protein-1 levels in type 1 (insulin-dependent) diabetic patients with peripheral neuropathy. Diabetologia 1992;35:868–872.
  118. Ishii DN: Neurobiology of insulin and insulin-like growth factors; in Loughlin SE, Fallon JH (eds): Neurotrophic Factors. New York, Academic Press, 1993, pp 415–442.
  119. Recio-Pinto E, Ishii DN: Insulin and related growth factors: Effects on the nervous system and mechanisms for neurite growth and regeneration. Neurochem Int 1988;12:397–414.
  120. Glazner GV, Lupien S, Miller JA, Ishii DN: Insulin-like growth factor II increased the rate of sciatic nerve regeneration in rats. Neuroscience 1993;54:791–797.
  121. Near SL, Whalen LR, Miller JA, Ishii DN: Insulin-like growth factor II stimulates motor nerve regeneration. Proc Natl Acad Sci USA 1992;89:11726–11720.

    External Resources

  122. Mill LF, Chao MV, Ishii DN: Insulin, insulin-like growth factor II, and nerve growth factor effects on tubulin mRNA levels and neurite formation. Proc Natl Acad Sci USA 1985;82:7126–7130.

    External Resources

  123. Feldman EL, Sullivan KA, Kim B, Russell JW: Insulin-like growth factors regulate neuronal differentiation and survival. Neurobiol Dis 1997;4:201–214.

    External Resources

  124. Russell JW, Feldman EL: Insulin-like growth factor-I prevents apoptosis in sympathetic neurons exposed to high glucose. Horm Metab Res 1999;31:90–96.
  125. Migdalis IN, Kalogeropoulou K, Kalantzis L, Nounopoulos C, Bouloukos A, Samartzis M: Insulin-like growth factor-I and IGF-I receptors in diabetic patients with neuropathy. Diabet Med 1995;12:823–827.
  126. Sharma K, Jin Y, Guo J, Ziyadeh FN: Neutralization of TGFβ by anti-TGFβ antibody attenuates kidney hypertrophy and the enhanced extracellular matrix gene expression in STZ-induced diabetic mice. Diabetes 1996;45:522–530.
  127. Border WA, Okuda S, Languino L: Suppression of experimental glomerulonephritis by antiserum against transforming growth factor β1. Nature 1990;346:371–374.
  128. Border WA, Noble NA, Yamamoto T: Natural inhibitor of transforming growth factor β protects against scarring in experimental kidney disease. Nature 1992;360:361–364.
  129. Mogyorosi A, Ziyadeh FN: Increased decorin mRNA in diabetic mouse kidney and in mesangial and tubular cells cultured in high glucose. Am J Physiol 1998;275:F827–F832.

    External Resources

  130. Flyvbjerg A, Frystyk J, Thorlacius-Ussing O: Somatostatin analogue administration prevents increase in somatomedin C and initial renal growth in diabetic and uninephrectomized rats. Diabetologia 1989;32:261–265.
  131. Serri O, Beauregard H, Brazeau P: Somatostatin analogue, octreotide, reduces increased glomerular filtration rate and kidney size in insulin dependent diabetes. JAMA 1991;265:888–892.
  132. Grant MB, Caballero S, Millard WB: Inhibition of IGF-I and b-FGF stimulated growth of human retinal endothelial cells by the somatostatin analogue, octreotide: A potential treatment for ocular neovascularization. Regul Pept 1993;48:267–278.
  133. Gilbert RE, Cox A, Wu LL, Allen TJ, Hulthen UL, Jerums G, Cooper ME: Expression of transforming growth factor factor β1 and type 4 collagen in the renal tubulointerstitium in experimental diabetes. Effects of ACE inhibition. Diabetes 1998;47:414–422.
  134. Skolnick AA: Novel therapies to prevent diabetic retinopathy. JAMA 1997;278:1480–1481.
  135. Ishii H, Tada H, Isogai S: An aldose reductase inhibitor prevents glucose-induced increase in transforming growth factor β and protein kinase C activity in cultured human mesangial cells. Diabetologia 1998;41:362–364.
  136. Tsuchida K, Makita Z, Yamagishi S, Miyoshi H, Obara S, Ishida M, Ishikawa S, Yasumura K, Koite T: Suppression of transforming growth factor beta and vascular endothelial growth factor in diabetic nephropathy in rats by a novel advanced glycation end product inhibitor, OPB-9195. Diabetologia 1999;42:579–588.
  137. D’Amato RJ, Loughnan MS, Flynn E: Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci USA 1994;91:4082–4085.
  138. O’Reilly MS, Holmgren L, Shing Y: Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastates by a Lewis lung carcinoma. Cell 1994;79:315–328.
  139. Simons M, Edelman ER, DeKeiser JL: Antisense C-myb oligonucleotides inhibit intimal arterial smooth muscle cell accumulation in vivo. Nature 1992;359:67–70.
  140. Bonn D: Blocking angionesis in diabetic retinopathy. Lancet 1996;348:604.
  141. Greene DA, Lattimer SA, Sima AA: Sorbitol, phosphoinositides, and sodium-potassium ATPase in the pathogenesis of diabetic complications. N Engl J Med 1987;316:599–606.
  142. Williamson JR, Chang K, Frangos M: Hyperglycemic pseudohypoxia and diabetic complications. Diabetes 1993;42:801–813.
  143. Lee TS, Saltsman KA, Ohashi H, King GL: Activation of protein kinase C by elevation of glucose concentration: Proposal for a mechanism in the development of diabetic vascular complications. Proc Natl Acad Sci USA 1989;86:5141–5145.
  144. De Rubertis FR, Craven PA: Activation of Protein Kinase C in glomerular cells in diabetes. Diabetes 1994;43:1–8.
  145. Giugliano D, Ceriello A, Paolisso G: Oxidative stress and diabetic vascular complications. Diabetes Care 1996;19:257–267.
  146. Ido Y, Kilo C, Williamson JR: Cytosolic NADH/NAD+, free radicals, and vascular dysfunction in early diabetes mellitus. Diabetologia 1997;40(suppl):115–117.
  147. Pertovaara L, Kaipainen A, Mustonen T: Vascular endothelial growth factor is induced in response to transforming growth factor-β in fibroblastic and epithelial cells. J Biol Chem 1994;269:6271–6274.
  148. Punglia R, Kuroki M, Tolentino MJ: VEGF mRNA and secreted protein in retinal cells. Invest Ophthalmol Vis Sci 1996;37(suppl):794.


Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50