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Vascular Endothelium and Diabetes Mellitus

  • Robert S. Bar

Abstract

Diabetes mellitus is a disease complex defined by abnormalities of glucose homeostasis and characterized by a group of chronic complications that affect the function of the eyes (retinopathy), kidneys (nephropathy), peripheral nerves (neuropathy), large blood vessels (atherosclerosis), and microvessels (microangiopathy). Indeed, the vascular dysfunction(s) in diabetes may underlie all of the chronic complications of the disease. These complications account for the vast majority of morbidity and mortality that accompanies diabetes, with atherosclerosis underlying the susceptibility to myocardial infarction and stroke, and the microvascular disease underlying retinopathy, nephropathy, and, perhaps, neuropathy. Diabetes mellitus is divided into two general categories, type I [insulin-dependent diabetes mellitus (IDDM)] and type II [non-insulin-dependent diabetes mellitus (NIDDM)]. The general characteristics of type I and type II diabetes are outlined in Table 1. Both type I and type II patients have similar complications, although the frequency of each complication differs between the two groups, with type I patients having a much greater incidence of microvascular complications (nephropathy and retinopathy) and type II patients having a somewhat higher frequency of microvascular complications that are associated with atherosclerosis. Although the precise etiologies of type I and II diabetes, as well as the causes of the diabetic complications, are not known, abnormalities of the vascular endothelium have been shown to occur early in the disease and have been implicated in the pathogenesis of chronic complications in this complex illness.

Keywords

Endothelial Cell Vascular Endothelium Human Endothelial Cell Aldose Reductase Vascular Basement Membrane 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Christrieb, A. R., 1973, Diabetes and hypertensive vascular disease. Mechanism and treatment, Am. J. Cardiol. 32:592–606.Google Scholar
  2. 2.
    Weidmann, P., Berreta-Piccoli, C., Keusch, G., Glück, Z., Mujagic, M., Grimm, M., Meier, A., and Ziegler, W. H., 1979, Sodium-volume factor, cardiovascular reactivity and hypotensive mechanism of diuretic therapy in mild hypertension associated with diabetes mellitus, Am. J. Med. 67:779–784.PubMedGoogle Scholar
  3. 3.
    Brody, M. J., and Dixon, R. L., 1964, Vascular reactivity in experimental diabetes mellitus, Circ. Res. 14: 494–501.PubMedGoogle Scholar
  4. 4.
    Pfaffman, M. A., Ball, C. R., Darby, A., and Hilman, R., 1982, Insulin reversal of diabetes-induced inhibition of vascular contractility in the rat, Am. J. Physiol. 242:H490–H495.Google Scholar
  5. 5.
    Scarborough, N. L., and Carrier, G. O., 1984, Nifedipine and alpha2-adrenoceptors in rat aorta. II. Role of extracellular calcium in enhanced alpha2-adrenoceptor-mediated contraction in diabetes, J. Pharmacol. Exp. Ther. 236:603–609.Google Scholar
  6. 6.
    Agrawal, D. K., and McNeill, J. H., 1987, Vascular responses to agonists in rat mesenteric artery from diabetic rats, Can. J. Physiol. Pharmacol. 65:1484–1490.PubMedGoogle Scholar
  7. 7.
    Head, R. J., Longhurst, P. A., Panek, R. L., and Stitzel, R. E., 1987, A contrasting effect of the diabetic state upon the contractile responses of aortic preparation from rat and rabbit, Br. J. Pharmacol. 91:275–286.PubMedGoogle Scholar
  8. 8.
    Kamata, K., Miyata, N., and Kasuya, Y., 1988, Mechanisms of increased responses of the aorta to α-adrenoceptor agonists in streptozotocin-induced diabetic rats, J. Pharmacobio-Dyn. 11:707–713.PubMedGoogle Scholar
  9. 9.
    Kamata, K., Miyata, N., and Kasuya, Y., 1989, Impairment of endothelium-dependent relaxation and changes in levels of cyclic GMP in aorta from streptozotocin-induced diabetic rats, Br. J. Pharmacol. 97:614–618.PubMedGoogle Scholar
  10. 10.
    Kamata, K., Miyata, N., and Kasuya, Y., 1989, Involvement of endothelial cells in relaxation and contraction responses of the aorta to isoproterenol in naive and streptozotocin-induced diabetic rats, J. Pharmacol. Exp. Ther. 249:890–894.PubMedGoogle Scholar
  11. 11.
    Pieper, G. M., and Gross, G. J., 1988, oxygen free radicals abolish endothelium-dependent relaxation in diabetic rat aorta, Am. J. Physiol. 225:H825–H833.Google Scholar
  12. 12.
    Mayhan, W. G., 1989, Impairment of endothelium-dependent dilatation of cerebral arterioles during diabetes mellitus, Am. J. Physiol. 256:H621–H625.Google Scholar
  13. 13.
    Gebremedhin, D., Koltai, M. Z., Pogatsa, G., Magyar, K., and Hadházy, P., 1987, Differential contractile responsiveness of femoral arteries from healthy and diabetic dogs: Role of endothelium, Arch. Int. Pharmacodyn. 288:100–108.PubMedGoogle Scholar
  14. 14.
    Fortes, Z. B., Leme, J. G., and Scivoletto, R., 1984, Vascular reactivity in diabetes mellitus: Possible role of insulin on the endothelial cell, Br. J. Pharmacol. 83:635–643.PubMedGoogle Scholar
  15. 15.
    Durante, W., Sen, A. K., and Sunahara, F. A., 1988, Impairment of endothelium-dependent relaxation in aortae from spontaneously diabetic rats, Br. J. Pharmacol. 94:463–468.PubMedGoogle Scholar
  16. 16.
    Gebremedhin, D., Koltai, M. Z., Pogatsa, G., Magyar, K., and Hadházy, P., 1988, Influence of experimental diabetes on the mechanical responses of canine coronary arteries: Role of endothelium, Cardiovasc. Res. 22:537–544.PubMedGoogle Scholar
  17. 17.
    de Tejada, I. S., Goldstein, I., Azadzoi, K., Krane, R. J., and Cohen, R. A., 1989, Impaired neurogenic and endothelium-mediated relaxation of penile smooth muscle from diabetic men with impotence, N. Engl. J. Med. 320:1025–1030.Google Scholar
  18. 18.
    Tanz, R. D., Chang, K. S. K., and Weiler, T. S., 1989, Histamine relaxation of aortic rings from diabetic rats, Agents Actions 28:1–8.PubMedGoogle Scholar
  19. 19.
    Van de Voorde, J., and Leusen, I., 1982, Vascular endothelium and the relaxation effect of histamine on aorta of the rat, Arch. Int. Pharmacodyn. 256:329–330.PubMedGoogle Scholar
  20. 20.
    Furchgott, R. F., and Zawadzki, J. V., 1980, The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine, Nature 288:373–376.PubMedGoogle Scholar
  21. 21.
    Furchgott, R. F., Zawadzki, J. V., and Cherry, P. D., 1981, Role of endothelium in the vasodilator response to acetylcholine, in: Vasodilation (R M. Vanhoutte, and I. Leusen, eds.), Raven Press, New York, pp. 49–66.Google Scholar
  22. 22.
    Cherry, P. D., Furchgott, R. F., Zawadzki, J. V., and Jothianandan, D., 1982, Role of endothelial cells in relaxation of isolated arteries by bradykinin, Proc. Natl. Acad. Sci. USA 79:2106–2110.PubMedGoogle Scholar
  23. 23.
    Chand, N., and Altura, B. M., 1981, Acetylcholine and bradykinin relax intrapulmonary arteries by acting on endothelial cells: Role in lung vascular diseases, Science 213:1376–1379.PubMedGoogle Scholar
  24. 24.
    Furchgott, R. F., 1983, Role of endothelium in responses of vascular smooth muscle, Circ. Res. 53:557–573.PubMedGoogle Scholar
  25. 25.
    Holzmann, S., 1982, Endothelium-induced relaxation by acetylcholine associated with larger rises in cyclic GMP in coronary arterial strips, J. Cyclic Nucleotide Res. 8:409–419.PubMedGoogle Scholar
  26. 26.
    Rapoport, R. M., and Murad, F., 1983, Agonist-induced endothelium-dependent relaxation in rat thoracic aorta may be mediated through cGMP, Circ. Res. 52:352–357.PubMedGoogle Scholar
  27. 27.
    Khan, M. T., and Furchgott, R. F., 1987, Similarities of behavior of nitric oxide (NO) and endothelium-derived relaxing factor in a perfusion cascade bioassay system, Fed. Proc. 46:385.Google Scholar
  28. 28.
    Palmer, R. M. J., Ferridge, A. G., and Moncada, S., 1987, Nitric oxide release accounts for the biological activity of endothelium derived relaxing factor, Nature 327:524–526.PubMedGoogle Scholar
  29. 29.
    Jayakody, L., Kappagoda, T., Senaratne, P. J., and Thomson, A. B., 1988, Impairment of endothelium-dependent relaxation: An early marker for atherosclerosis in the rabbit, Br. J. Pharmacol. 94:335–346.PubMedGoogle Scholar
  30. 30.
    Sim, M. K., and Singh, M., 1987, Decreased responsiveness of the aortae of hypertensive rats to acetylcholine, histamine and noradrenaline, Br. J. Pharmacol. 90:147–150.PubMedGoogle Scholar
  31. 31.
    Zelechowska, M. G., von Mourik, J. A., and Brodniewicz-Proba, T., 1985, Ultrastructural localization of factor VIII procoagulant antigen in human liver hepatocytes, Nature 317:729–738.PubMedGoogle Scholar
  32. 32.
    Wion, K. L., Kelly, D., Summerfield, J. A., Tuddenham, E. G., and Lawn, R. M., 1985, Distribution of factor VIII mRNA and antigen in human liver and other tissues, Nature 317:726–729.PubMedGoogle Scholar
  33. 33.
    Banga, J. D., and Sixma, J. J., 1986, Diabetes mellitus, vascular disease and thrombosis, Clin. Haematol. 15: 465–492.PubMedGoogle Scholar
  34. 34.
    Jaffe, E. A., Hoyer, L. W., and Nachman, R. L., 1974, Synthesis of von Willebrand factor by cultured human endothelial cells, Proc. Natl. Acad. Sci. USA 71:1906–1909.PubMedGoogle Scholar
  35. 35.
    Bloom, A. L., 1979, The synthesis of factor VIII, Clin. Haematol. 8:53–76.PubMedGoogle Scholar
  36. 36.
    Nachman, R., Levine, R., and Jaffe, E. A., 1977, Synthesis of factor VIII antigen by cultured guinea pig megakaryocytes, J. Clin. Invest. 60:914–921.PubMedGoogle Scholar
  37. 37.
    Tschopp, T. P., Weiss, H. J., and Baumgartner, H. R., 1974, Decreased adhesion of platelets to subendothelium in von Willebrand’s disease, J. Lab. Clin. Med. 83:296–300.PubMedGoogle Scholar
  38. 38.
    Sakariassen, K. S., Bolhuis, P. A., and Sixma, J. J., 1979, Human blood platelet adhesion to artery subendothelium is mediated by factor VIII-von Willebrand factor bound to the subendothelium, Nature 279:636–638.PubMedGoogle Scholar
  39. 39.
    Turitto, V. T., Weiss, H. J., and Baumgartner, H.R., 1984, Platelet interaction with rabbit subendothelium in von Willebrand’s disease: Altered thrombus formation distinct from platelet adhesion, J. Clin. Invest. 74: 1730–1741.PubMedGoogle Scholar
  40. 40.
    Colwell, J. A., Lopes-Virella, M., Winocour, P. D., and Halushka, P. V., 1988, New concepts about the pathogenesis of atherosclerosis in diabetes mellitus, in: The Diabetic Foot (M. E. Levin and L. W. O’Neal, eds.), Mosby, St. Louis, pp. 51–70.Google Scholar
  41. 41.
    Colwell, J. A., Lopes-Virella, M., and Halushka, P. V., 1981, Pathogenesis of atherosclerosis in diabetes mellitus, Diabetes Care 4:121–133.PubMedGoogle Scholar
  42. 42.
    Porta, M., Ricchetii, I., la Selva, M., Bertagna, A., and Molinatti, G. M., 1984, Quantitative and qualitative assessment of plasma von Willebrand factor variations, as induced by forearm venous stasis in patients with diabetic microangiopathy, Diabetes Res. 1:219–221.PubMedGoogle Scholar
  43. 43.
    Gonzalez, J., Colwell, J. A., Sarji, K. E., and Nair, R. ML, 1980, Effect of metabolic control with insulin on plasma von Willebrand factor activity (VIIIR:WF) in diabetes mellitus, Thromb. Res. 17:261–266.PubMedGoogle Scholar
  44. 44.
    Winocour, P. D., Lopes-Virella, M., Laimins, M., and Colwell, J. A., 1983, Time course of changes in in vitro platelet function and plasma von Willebrand factor activity (VIIIR:WF) and factor VIII-related antigen (VIIIR:Ag) in the diabetic rat, J. Lab. Clin. Med. 102:795–804.PubMedGoogle Scholar
  45. 45.
    Aanderud, S., Krane, H., and Nordoy, A., 1985, Influence of glucose, insulin and sera from diabetic patients on the prostacyclin synthesis in vitro in cultured human endothelial cells, Diabetologia 28:641–644.PubMedGoogle Scholar
  46. 46.
    Umeda, F., Inoguchi, T., and Nawata, H., 1989, Reduced stimulatory activity on prostacyclin production by cultured endothelial cells in serum from aged and diabetic patients, Atherosclerosis 75:61–66.PubMedGoogle Scholar
  47. 47.
    Colwell, J. A., and Lopes-Virella, M. F., 1988, A review of the development of large-vessel disease in diabetes mellitus, Am. J. Med. 85(Suppl. 5A):113–118.PubMedGoogle Scholar
  48. 48.
    Colwell, J. A., Winocour, P. D., Lopes-Virella, M., and Halushka, P. V., 1983, New concepts about the pathogenesis of atherosclerosis in diabetes mellitus, Am. J. Med. 75:67–80.PubMedGoogle Scholar
  49. 49.
    Porta, M., la Selva, M., Molinatti, P., and Molinatti, G. M., 1987, Endothelial cell function in diabetic microangiopathy, Diabetologia 30:601–609.PubMedGoogle Scholar
  50. 50.
    Stout, R. W., 1982, Glucose inhibits replication of cultured human endothelial cells, Diabetologia 23:436–439.PubMedGoogle Scholar
  51. 51.
    Lorenzi, M., Caghero, E., Toledo, S., 1985, Glucose Toxicity for human endothelial cells in culture: Delayed replication, disturbed cell cycle, and accelerated death, Diabetes 34:621–627.PubMedGoogle Scholar
  52. 52.
    Weimann, B. J., Lorch, E., and Baumgartner, H. R., 1984, High glucose concentrations do not influence replication and prostacyclin release of human endothelial cells, Diabetologia 27:62–63.PubMedGoogle Scholar
  53. 53.
    Lorenzi, M., Caghero, E., and Toledo, S., 1985, Glucose toxicity for human endothelial cells in culture: Delayed replication, disturbed cell cycle, and accelerated death, Diabetes 34:621–627.PubMedGoogle Scholar
  54. 54.
    Gillion, K. R. W., and Hawthorne, J. N., 1983, Transport of myo-inositol in endoneurial preparations of sciatic nerve from normal and streptozotocin-diabetic rats, Biochemistry 210:775–781.Google Scholar
  55. 55.
    Yorek, M. A., and Dunlap, J. A., 1989, The effect of elevated glucose levels on myo-inositol metabolism in cultured bovine aortic endothelial cells, Metabolism 38:16–22.PubMedGoogle Scholar
  56. 56.
    Mordes, D. B., Lazarchick, J., Colwell, J. A., and Sens, D. A., 1983, Elevated glucose concentrations increase factor VIIIR:Ag levels in human umbilical vein endothelial cells, Diabetes 32:876–878.PubMedGoogle Scholar
  57. 57.
    Williams, S. K., Devenny, J. J., and Bitensky, M. W., 1981, Micropinocytic ingestion of glycosylated albumin by isolated microvessels: Possible role in pathogenesis of diabetic microangiopathy, Proc. Natl. Acad. Sci. USA 78:2393–2397.PubMedGoogle Scholar
  58. 58.
    Lorenzi, M., Caghero, E., Markey, B., Henriksen, T., Witztum, J. L., and Sampietro, T., 1984, Interaction of human endothelial cells with elevated glucose concentrations and native and glycosylated low density lipoproteins, Diabetologia 26:218–222.PubMedGoogle Scholar
  59. 59.
    Sussman, I., Carson, M. P., Schultz, V., Wu, X. P., McCall, A. L., Ruderman, N. B., and Thornheim, K., 1988, Chronic exposure to high glucose decreases myo-inositol in cultured cerebral microvascular pericytes but not in endothelium, Diabetologia 31:771–775.PubMedGoogle Scholar
  60. 60.
    Winegrad, A. I., 1987, Does a common mechanism induce the diverse complications of diabetes? Diabetes 36:396–406.PubMedGoogle Scholar
  61. 61.
    Greene, D. A., Lattimer, S. A., and Sima, A. A. F., 1987, Sorbitol, phosphoinositides, and sodium-potassium-ATPase in the pathogenesis of diabetic complications, N. Engl. J. Med. 316:599–606.PubMedGoogle Scholar
  62. 62.
    Gabbay, K. H., 1973, The sorbitol pathway and the complications of diabetes, N. Engl. J. Med. 288: 831–836.PubMedGoogle Scholar
  63. 63.
    Kennedy, A., Frank, R. N., and Varma, S. D., 1983, Aldose reductase activity in retinal and cerebral microvessels and cultured vascular cells, Invest. Ophthalmol. Vis. Sci. 24:1250–1258.PubMedGoogle Scholar
  64. 64.
    Ludvigson, M. A., and Sorenson, R. L., 1980, Immunohistochemical localization of aldose reductase. II. Rat eye and kidney, Diabetes 29:450–459.PubMedGoogle Scholar
  65. 65.
    Lorenzi, M., Toledo, S., Boss, G. R., Lane, M. J., and Montisano, D. F., 1987, The polyol pathway and glucose 6-phosphate in human endothelial cells cultured in high glucose concentrations, Diabetologia 30:222–227.PubMedGoogle Scholar
  66. 66.
    Williamson, J. R., Chang, K., Rowold, E., Marvel, J., Tomlinson, M., Sherman, W.R., Ackerman, K.E., and Kilo, C., 1985, Sorbinil prevents diabetes-induced increases in vascular permeability but does not alter collagen cross-linking, Diabetes 34:703–705.PubMedGoogle Scholar
  67. 67.
    Li, W., Khatami, M., and Rockey, J. H., 1985, The effects of glucose and an aldose reductase inhibitor on the sorbitol and collagen synthesis of bovine retinal capillary pericytes in culture, Exp. Eye Res. 40: 439–444.PubMedGoogle Scholar
  68. 68.
    Gundersen, H. J. G., and Christensen, N. J., 1977, Intravenous insulin causing loss of intravascular water and albumin and increased adrenergic nervous activity in diabetics, Diabetes 26:551–557.PubMedGoogle Scholar
  69. 69.
    Siperstein, M. D., Unger, R. H., and Madison, L. L., 1968, Studies of capillary basement membranes in normal subjects, diabetic, and prediabetic patients, J. Clin. Invest. 47:1973–1999.PubMedGoogle Scholar
  70. 70.
    Vracko, R., 1970, Skeletal muscle capillaries in diabetics: A quantitative analysis, Circulation 41:271–284.PubMedGoogle Scholar
  71. 71.
    Bloodworth, J. M. B., Jr., Engerman, R. L., and Powers, K. L., 1969, Experimental diabetic microangiopathy. I. Basement membrane statistics in the dog, Diabetes 18:455–458.PubMedGoogle Scholar
  72. 72.
    Osterby Hansen, R., and Lundback, K., 1970, The basement membrane morphology in diabetes mellitus, in: Diabetes Mellitus: Theory and Practice (M. Ellenbert and H. Rifkin, eds.), McGraw-Hill, New York, pp. 178–209.Google Scholar
  73. 73.
    Williamson, J.R., and Kilo, C., 1976, Basement-membrane thickening and diabetic microangiopathy, Diabetes 25(Suppl. 2):925–927.PubMedGoogle Scholar
  74. 74.
    Beisswenger, F. J., and Spiro, R. G., 1970, Human glomerular basement membrane: Chemical alteration in diabetes mellitus, Science 168:596–598.PubMedGoogle Scholar
  75. 75.
    Kramer, R. H., Fuh, G. M., and Bensch, K. G., 1985, Synthesis of extracellular matrix glycoproteins by cultured endothelial cells, J. Cell. Physiol. 123:1–9.PubMedGoogle Scholar
  76. 76.
    Bar, R. S., Dake, B. L., and Spanheimer, R. G., 1985, Sulfated glycosaminoglycans in cultured endothelial cells from capillaries and large vessels of human and bovine origin, Atherosclerosis 56:11–26.PubMedGoogle Scholar
  77. 77.
    Bar, R. S., Dake, B. L., and Stueck, S., 1987, Stimulation of proteoglycans by IGF-I and IGF-II in microvessel and large vessel endothelial cells, Am. J. Physiol. 253:E21–E27.Google Scholar
  78. 78.
    McAuslan, B. R., Hannan, G. N., Reilly, W., and Stewart, F. H., 1980, Variant endothelial cells. Fibronectin as a transducer of signals for migration and neovascularization, J. Cell. Physiol. 104:177–186.PubMedGoogle Scholar
  79. 79.
    Garcia, L. J., Hamamura, L., Migliorini, R. H., and Leite, M. P., 1973, Influence of diabetes upon the inflammatory response of the rat. A pharmacological analysis, Eur. J. Pharmacol. 23:74–81.Google Scholar
  80. 80.
    Llorach, M. A. S., Bohm, G. M., and Garcia, L. J., 1976, Decreased vascular reaction to permeability factors in experimental diabetes, Br. J. Exp. Pathol. 57:747–754.PubMedGoogle Scholar
  81. 81.
    Osterby, R., Gundersen, H. J., and Christensen, N. J., 1978, The acute effect of insulin on capillary endothelial cells, Diabetes 27:745–749.PubMedGoogle Scholar
  82. 82.
    Fortes, Z. B., Lerne, J. G., and Scivoletto, R., 1983, Vascular reactivity in diabetes mellitus: Role of the endothelial cell, Br. J. Pharmacol. 79:771–781.PubMedGoogle Scholar
  83. 83.
    Orlidge, A., and Hollis, T. M., 1982, Aortic endothelial and smooth muscle histamine metabolism in experimental diabetes, Arteriosclerosis 2:142–150.PubMedGoogle Scholar
  84. 84.
    Hollis, T. M., Gallik, S. G., Olidge, A., et al., 1983, Aortic endothelial and smooth muscle histamine metabolism, Arteriosclerosis 3:599–606.PubMedGoogle Scholar
  85. 85.
    Stevens, V J., Rouzer, C. A., Monnier, V.M., and Cerami, A., 1978, Diabetic cataract formation: Potential role of glycosylation of lens crystallins, Proc. Natl. Acad. Sci. USA 75:2918–2922.PubMedGoogle Scholar
  86. 86.
    Day, J. F., Ingebretsen, C. G., Ingebretsen, W. R., Jr., Baynes, J. W., and Thorpe, S. R., 1980, Nonenzymatic glycosylation of serum proteins and hemoglobin: Response to changes in blood glucose levels in diabetic rats, Diabetes 29:524–527.PubMedGoogle Scholar
  87. 87.
    Brownlee, M., and Cerami, A., 1981, The biochemistry of the complications of diabetes mellitus, Annu. Rev. Biochem. 50:385–432.PubMedGoogle Scholar
  88. 88.
    Witztum, J. L., Steinbrecher, U. P., Fisher, M., and Kesaniemi, A., 1983, Nonenzymatic glucosylation of homologous low density lipoprotein and albumin renders them immunogenic in the guinea pig, Proc. Natl. Acad. Sci. USA 80:2757–2761.PubMedGoogle Scholar
  89. 89.
    Brownlee, M., Cerami, A., and Vlassara, H., 1988, Advanced products of nonenzymatic glycation and the pathogenesis of diabetic vascular disease, Diabetes Metab. Rev. 4:437–451.PubMedGoogle Scholar
  90. 90.
    Bendayan, H., and Rasio, E. A., 1981, Hyperglycemia and microangiopathy in the eel, Diabetes 30:317–325.PubMedGoogle Scholar
  91. 91.
    Bar, R. S., Lowe, W. L., and Spanheimer, R. G., 1989, Interactions of insulin and IGFs with cellular components of the arterial wall: potential impact on atherosclerosis, in: Molecular and Cellular Biology of Insulin-like Growth Factors and Their Receptors, (D. LeRoith and M. K. Raizada, eds.), Plenum Press, New York, pp. 473–484.Google Scholar
  92. 92.
    Bar, R. S., Boes, M., Dake, B. L., Henley, S. A., and Booth, B. A., 1990, Receptor-mediated transport of circulating insulin and IGF by vascular endothelium, in: Endothelial Cell Function in Diabetic Microangiopathy: Problems in Methodology and Clinical Aspects. Frontiers in Diabetes, Vol. 9 (G. M. Molinatti, R. S. Bar, F. Belfiore, and M. Porta, eds.), Karger, Basel, pp. 97–107.Google Scholar
  93. 93.
    Bar, R. S., Boes, M., Dake, B., Booth, B., Henley, S. A., and Sandra, A., 1988, Insulin, IGFs and vascular endothelium, Am. J. Med. 85(5A):59–70.PubMedGoogle Scholar
  94. 94.
    Bar, R. S., 1984, Receptors for insulin and multiplication stimulating activity (MSA) in endothelial cells, in: Biology of Endothelial Cells (E. A. Jaffe, ed.), Nijhoff, The Hague.Google Scholar
  95. 95.
    Bar, R. S., Boes, M., Dake, B. L., Henley, S., and Sandra, A., 1988, Vascular endothelium and the IGFs, in: Diabetes1988 (R. G. Larkins, P. Z. Zimmet, and D. J. Chisholm, eds.), Elsevier Science Publishers, B.V., pp. 151–154.Google Scholar
  96. 96.
    Bar, R. S., Hoak, J. C., and Peacock, M. L., 1978, Insulin receptors in human endothelial cells: Identification and characterization, J. Clin Endocrinol. Metab. 47:699–702.PubMedGoogle Scholar
  97. 97.
    Bar, R. S., Peacock, M. L., Spanheimer, R. G., Veenstra, R., and Hoak, J. C., 1980, Differential binding of insulin to human arterial and venous endothelial cells in primary culture, Diabetes 29:991–995.PubMedGoogle Scholar
  98. 98.
    Peacock, M. L., Bar, R. S., and Goldsmith, J. C., 1982, Interactions of insulin with bovine endothelium, Metabolism 31:52–56.PubMedGoogle Scholar
  99. 99.
    Bar, R. S., and Boes, M., 1984, Distinct receptors for IGF-I, IGF-II, and insulin are present on bovine capillary endothelial cells and large vessel endothelial cells, Biochem. Biophys. Res. Commun.124: 203–209.PubMedGoogle Scholar
  100. 100.
    King, G. L., Buzney, S., Kahn, C. R., Hetu, N., Buchwald, S., Macdonald, S.G., and Rand, L. I., 1983, Differential responsiveness to insulin in endothelial and support cells from micro-and macrovessels, J. Clin. Invest. 71:974–979.PubMedGoogle Scholar
  101. 101.
    Bar, R. S., Goldsmith, J.C., and Owen, W. G., 1982, Properties of endothelial cells in culture: Recent studies, Lymphokines 7:249–271.Google Scholar
  102. 102.
    Bar, R. S., Dolash, S., Dake, B. L., and Boes, M., 1986, Cultured capillary endothelial cells from bovine adipose tissue: A model for insulin binding and action in microvascular endothelium, Metabolism 35: 317–322.PubMedGoogle Scholar
  103. 103.
    King, G. L., Goodman, A. D., Buzney, S., Moses, A., and Kahn, C. R., 1985, Receptors and growth-promoting effects of insulin and insulin-like growth factors on cells from bovine and retinal capillaries and aorta, J. Clin. Invest. 75:1028–1036.PubMedGoogle Scholar
  104. 104.
    Frank, H. J. L., and Partridge, W. M., 1981, A direct in vitro demonstration of insulin biding to isolated brain microvessels, Diabetes 30:757–761.PubMedGoogle Scholar
  105. 105.
    Pillion, D. J., Haskell, J. F., and Meezan, F., 1982, Cerebral cortical microvessels: An insulin sensitive tissue, Biochem. Biophys. Res. Commun. 104:686–692.PubMedGoogle Scholar
  106. 106.
    Bar, R. S., DeRose, A., Sandra, A., Peacock, M. L., and Owen, W. G., 1983, Insulin binding to microvascular endothelium of intact heart: A kinetic and morphometric analysis, Am. J. Physiol. 244:E447–E452.Google Scholar
  107. 107.
    Bar, R. S., Boes, M., and Sandra, A., 1985, Receptors of insulin-like growth factor I (IGF-I) in myocardial capillary endothelium of the intact perfused heart, Biochem. Biophys. Res. Commun. 133:724–730.PubMedGoogle Scholar
  108. 108.
    Bar, R. S., Boes, M., and Sandra, A., 1988, IGF receptors in myocardial capillary endothelium: Potential regulation of IGF-I transport to cardiac muscle, Biochem. Biophys. Res. Commun. 152:93–98.PubMedGoogle Scholar
  109. 109.
    Bar, R. S., Boes, M., and Sandra, A., 1988, Vascular transport of insulin to rat cardiac muscle: Central role of the capillary endothelium, J. Clin. Invest. 81:1225–1233.PubMedGoogle Scholar
  110. 110.
    van Houten, M., and Posner, B. I., 1979, Insulin binds to brain blood vessels in vivo, Nature 282:623–625.Google Scholar
  111. 111.
    Jonas, H.A., Newman, J. D., and Harrison, L. C., 1986, An atypical insulin receptor with high affinity for insulin-like growth factors copurified with placental insulin receptor, Proc. Natl. Acad. Sci. USA 83:4124–4128.PubMedGoogle Scholar
  112. 112.
    Moxham, K., Duronio, V., and Jacobs, S., 1989, Insulin-like growth factor I receptor β subunit heterogeneity, J. Biol. Chem. 264:13238–13244.PubMedGoogle Scholar
  113. 113.
    Treadway, J., Morrison, B.D., Goldpine, I., and Pessin, J. E., 1989, Assembly of insulin/insulin-like growth factor I hybrid receptors in vitro, J. Biol. Chem. 264:21450–21453.Google Scholar
  114. 114.
    Cox, A. J., Bar, R. S., Jonas, H. A., and Newman, J. D., 1987, Atypical receptors for insulin-like peptides in endothelial cells, Diabetes 36:54A.Google Scholar
  115. 115.
    Bar, R. S., Harrison, L. C., Baxter, R. C., Boes, M., Dake, B.L., Booth, B., and Cox, A., 1987, Production of IGF-binding proteins by vascular endothelial cells, Biochem. Biophys. Res. Commun. 148:734–739.PubMedGoogle Scholar
  116. 116.
    Bar, R. S., Booth, B. A., Boes, M., and Dake, B. L., 1989, Insulin-like growth factor-binding proteins from vascular endothelial cells: Purification, characterization and intrinsic biological activities, Endocrinology 125:1910–1920.PubMedGoogle Scholar
  117. 117.
    King, G. L., Buzney, S., Kahn, C. R., Hetu, N., Buchwald, S., Macdonald, S. G., and Rand, L. I., 1983, Differential binding of insulin to human arterial and venous endothelial cells in primary culture, J. Clin. Invest. 71:974–979.PubMedGoogle Scholar
  118. 118.
    King, G. L., Goodman, A. D., Buzney, S., Moses, A., and Kahn, C. R., 1985, Receptors and growth-promoting effects of insulin and insulin-like growth factors on cells from bovine retinal capillaries and aorta, J. Clin. Invest. 75:1028–1036.PubMedGoogle Scholar
  119. 119.
    Gerritsen, M. E., and Burke, T. M., 1985, Insulin binding and effects of insulin on glucose uptake and metabolism in cultured rabbit coronary microvessel endothelium, Proc. Soc. Exp. Biol. Med. 180:17–23.PubMedGoogle Scholar
  120. 120.
    Vinters, H. V., Berliner, J. A., Beck, D. W., Maxwell, K., Bready, J. V., and Cancilla, P., 1985, Insulin stimulates DNA synthesis in cerebral microvessel endothelium and smooth muscle, Diabetes 34:964–969.PubMedGoogle Scholar
  121. 121.
    Bar, R. S., Siddle, K., Dolash, S., Boes, M., and Dake, B., 1988, Actions of insulin and insulin-like growth factors I and II in cultured capillary endothelial cells from bovine adipose tissue, Metabolism 37:714–720.PubMedGoogle Scholar
  122. 122.
    Bar, R. S., Stueck, S., Dake, B. L., and Spanheimer, R. G., 1984, Multiplication stimulating activity (MSA) specifically augments proteoglycan synthesis in cultured endothelial cells, Endocrinology 115:2487–2489.PubMedGoogle Scholar
  123. 123.
    Bar, R. S., Dake, B. L., and Stueck, S., 1987, Stimulation of proteoglycans by IGF-I and IGF-II in microvessel and large vessel endothelial cells, Am. J. Physiol. 253:E21–E27.Google Scholar
  124. 124.
    Boes, M., Dake, B. L., and Bar, R. S., 1991, Interactions of cultured endothelial cells with TGF-β, bFGF, PDGF and IGF-I, Life Sciences 48:811–821.PubMedGoogle Scholar
  125. 125.
    Bar, R. S., Boes, M., Booth, B. A., Dake, B. L., Henley S., and Hart, M. N., 1989, The effects of platelet-derived growth factor (PDGF) in cultured microvessel endothelial cells, Endocrinology 124:1841–1848.PubMedGoogle Scholar
  126. 126.
    Vlodavsky, I., Fridman, R., Sullivan, R., Sasse, J., and Klagsbrun, M., 1987, Aortic endothelial cells synthesize basic fibroblast growth factor which remains cell associated and platelet-derived growth factorlike protein which is secreted, J. Cell. Physiol. 131:402–408.PubMedGoogle Scholar
  127. 127.
    Hannan, R. L., Kourembanas, S., Flanders, K., Rogelj, S. J., Roberts, A. B., Faller, D. V., and Klagsbrun, M., 1988, Endothelial cells synthesize basic fibroblast growth factor and transforming growth factor beta, Growth Factors 1:1–17.Google Scholar
  128. 128.
    Kourembanas S., and Faller, D. V., 1989, Platelet-derived growth factor production by human umbilical vein endothelial cells is regulated by basic fibroblast growth factor, J. Biol. Chem. 264:4456–4459.PubMedGoogle Scholar
  129. 129.
    Dernovsek, K. D., Bar, R. S., Ginsberg, B. H., and Lioubin, M. N., 1984, Rapid transport of biologically intact insulin through cultured endothelial cells, J. Clin. Endocrinol. Metab. 58:761–763.PubMedGoogle Scholar
  130. 130.
    Dernovsek, K. D., and Bar, R. S., 1985, Processing of cell-bound insulin by capillary and macrovascular endothelial cells in culture, Am. J. Physiol. 248:E244–E251.Google Scholar
  131. 131.
    Jialal, I., King, G. L., and Buchwald, S., 1984, Processing of insulin by bovine endothelial cells in culture: Internalization without degradation, Diabetes 33:794–800.PubMedGoogle Scholar
  132. 132.
    Bar, R. S., Boes, M., and Yorek, M., 1986, Processing of insulin-like growth factors I and II by capillary and large vessel endothelial cells, Endocrinology 118:1072–1080.PubMedGoogle Scholar
  133. 133.
    Bar, R. S., Boes, M., and Sandra, A., 1988, Vascular transport of insulin to rat cardiac muscle: Central role of the capillary endothelium, J. Clin. Invest. 81:1225–1233.PubMedGoogle Scholar
  134. 134.
    Bar, R. S., Boes, M., and Sandra, A., 1988, IGF receptors in myocardial capillary endothelium: Potential regulation of IGF-I transport to cardiac muscle, Biochem. Biophys. Res. Commun. 152:93–98.PubMedGoogle Scholar
  135. 135.
    Van Wyk, J. J., Underwood, L. E., Hintz, R. L., Clemmons, D. R., Viona, S. J., and Weaver, R. P., 1974, The somatomedins: A family of insulin-like hormones under growth hormone control, Recent Prog. Horm. Res. 30:259–318.PubMedGoogle Scholar
  136. 136.
    Froesch, E. R., Schmid, D., Schwander, J., and Zapf, J., 1985, Actions of insulin-like growth factors, Annu. Rev. Physiol. 47:443–467.PubMedGoogle Scholar
  137. 137.
    Zapf, J., and Foresch, E. R., 1986, Insulin-like growth factors/somatomedins: Structure, secretion, biological actions and physiological role, Horm. Res. 24:121–130.PubMedGoogle Scholar
  138. 138.
    Baxter, R. C., and Martin, J. L., 1989, Binding proteins for the insulin-like growth factors: Structure, regulation and function, Prog. Growth Factor Res. 1:49–68.PubMedGoogle Scholar
  139. 139.
    D’Ercole, A. J., Applewhite, G. T., and Underwood, L. E., 1980, Evidence that somatomedin is synthesized by multiple tissues in the fetus, Dev. Biol. 73:315–328.Google Scholar
  140. 140.
    Clemmons, D. R., Underwood, L. E., and Van Wyk, J. J., 1981, Hormonal control of immunoreactive somatomedin production by cultured human fibroblasts, J. Clin. Invest. 67:10–19.PubMedGoogle Scholar
  141. 141.
    Moses, A. C., Frienkel, A. J., Knowles, B. B., and Aden, D. P., 1983, Demonstration that a human hepatoma cell line produces a specific insulin-like growth factor carrier protein, J. Clin. Endocrinol. Metab. 56:1003–1008.PubMedGoogle Scholar
  142. 142.
    Romanus, J. A., Yang, Y. W.-H., Nissley, S. P., and Rechler, M. M., 1987, Biosynthesis of the low molecular weight carrier protein for the insulin-like growth factor in rat liver and fibroblasts, Endocrinology 121:1041–1050.PubMedGoogle Scholar
  143. 143.
    McCusker, R. H., and Clemmons, D. R., 1988, Insulin-like growth factor binding protein and secretion by muscle cells: Effects of cellular differentiation and proliferation, J. Cell. Physiol. 137:505–512.PubMedGoogle Scholar
  144. 144.
    D’Ercole, A. J., Stiles, A. D., and Underwood, L. E., 1984, Tissue concentrations of somatomedin C: Further evidence for multiple sites of synthesis and paracrine or autocrine mechanisms of action, Proc. Natl. Acad. Sci. USA 81:935–939.PubMedGoogle Scholar
  145. 145.
    Booth, B. A., Bar, R. S., Boes, M., Dake, B. L., Bayne, M., and Cascieri, M., 1990, Intrinsic bioactivity of IGF-binding proteins from vascular endothelial cells, Endocrinology 127:2630–2638.PubMedGoogle Scholar
  146. 146.
    Bar, R. S., Clemmons, D. R., Boes, M., Busby, W. H., Booth, B. A., Dake, B. L., and Sandra, A., 1990, Transcapillary permeability and subendothelial distribution of endothelial and amniotic fluid insulin-like growth factor binding proteins in the rat heart, Endocrinology 127:1078–1086.PubMedGoogle Scholar
  147. 147.
    Bar, R. S., Boes, M., Dake, B., Booth, B., Busby, W. H., and Sandra, A., 1990, Transcapillary permeability of IGF-binding proteins (abstract 286), p. 96, in: Endocrine Society 72nd Annual Meeting (June 20–23, 1990) Programme and Abstracts.Google Scholar
  148. 148.
    Suikkari, A.-M., Koivisto, V. A., Rutanen, E.-M., Yki-Järvinen, H., Karonen, S. L., and Seppälä, M., 1988, Insulin regulates the serum levels of low molecular weight insulin-like growth factor-binding protein, J. Clin. Endocrinol. Metab. 66:266–272.PubMedGoogle Scholar
  149. 149.
    Suikkari, A.-M., Koivisto, V. A., Koistinen, R., Seppala, M., and Yki-Järvinen, H., 1989, Dose-response characteristics for suppression of low molecular weight plasma insulin-like growth factor-binding protein by insulin, J. Clin. Endocrinol. Metab. 68:135–140.PubMedGoogle Scholar
  150. 150.
    Wautier, J. L., Paton, R. C., Wautier, M. P., Pintigny, D., Abadie, E., Passa, P., and Caen, J. P., 1981, Increased adhesion of erythrocytes of endothelial cells in diabetes mellitus and its relation to vascular complications, N. Engl. J. Med. 305:237–242.PubMedGoogle Scholar
  151. 151.
    Schmid-Schonbein, H., and Volger, E., 1976, Red-cell aggregation and red-cell deformability in diabetes, Diabetes 25(Suppl. 2):897–902.PubMedGoogle Scholar
  152. 152.
    Barnes, A. J., Locke, P., Scudder, P. R., Dormandy, T. L., Dormandy, J. A., and Slack, J., 1977, Is hyperviscosity a treatable component of diabetic microcirculatory disease? Lancet 2:789–791.PubMedGoogle Scholar
  153. 153.
    McMillan, D. E., Utterback, N. G., and La Puma, J., 1978, Reduced erythrocyte deformability in diabetes, Diabetes 27:895–901.PubMedGoogle Scholar
  154. 154.
    Wali, R. K., Jaffe, S., Kumar, D., and Kalra, V. K., 1988, Alterations in organization of phospholipids in erythrocytes as factors in adherence to endothelial cells in diabetes mellitus, Diabetes 37:104–111.PubMedGoogle Scholar
  155. 155.
    Wautier, J. L., Wautier, M. P., Pintigny, D., Galacteros, F., Courillon, A., Passa, P., and Caen, J. P., 1983, Factors involved in cell adhesion to vascular endothelium, Blood Cells 9:221–234.PubMedGoogle Scholar
  156. 156.
    Colwell, J. A., Winocour, P. D., and Halushka, P. V., 1983, Do platelets have anything to do with diabetic microvascular disease? Diabetes 32(Suppl. 2):14–19.PubMedGoogle Scholar
  157. 157.
    Berliner, J. A., Frank, H. J. L., Karasic, D., and Capdeville, M., 1984, Lipoprotein-induced insulin resistance in aortic endothelium, Diabetes 33:1039–1044.PubMedGoogle Scholar
  158. 158.
    Fielding, C. J., 1981, The endothelium, triglyceride-rich lipoproteins, and atherosclerosis: Insights from cell biology and lipid metabolism, Diabetes 30(Suppl. 2): 19–23.PubMedGoogle Scholar
  159. 159.
    Ramirez, I., and Severson, D. L., 1986, Effect of diabetes on acid and neutral triacylglycerol lipase and on lipoprotein lipase activities in isolated myocardial cells from rat heart, Biochem. J., 238:233–238.PubMedGoogle Scholar
  160. 160.
    Yee, R. W., Matsuda, M., Kern, T. S., Engerman, R. L., and Edelhauser, H. F., 1985, Corneal endothelial changes in diabetic dogs, Curr. Eye Res. 4:759–766.PubMedGoogle Scholar
  161. 161.
    Sharma, N. K., Gardiner, T. A., and Archer, D. B., 1985, A morphologic and autoradiographic study of cell death and regeneration in the retinal microvasculature of normal and diabetic rats, Am. J. Ophthalmol. 100: 51–60.PubMedGoogle Scholar
  162. 162.
    Itoi, M., Nakamura, T., Mizobe, K., Kodama, Y., Nakagawa, N., and Itoi, M., 1989, Specular microscopic studies of the corneal endothelia of Japanese diabetics, Cornea 8:2–6.PubMedGoogle Scholar
  163. 163.
    Busted, N., Olsen, T., and Schmitz, O., 1981, Clinical observations on the corneal thickness and the corneal endothelium in diabetes mellitus, Br. J. Ophthalmol. 65:637–690.Google Scholar
  164. 164.
    Schultz, R. O., Matsuda, M., and Yee, R. W., 1984, Corneal endothelial changes in type I and type II diabetes mellitus, Am. J. Ophthalmol. 98:401–410.PubMedGoogle Scholar
  165. 165.
    Moore, S. A., Bohlen, H. G., Miller, B. G., and Evans, A. P., 1985, Cellular and vessel wall morphology of cerebral cortical arterioles after short-term diabetes in adult rats, Blood Vessels 22:265–277.PubMedGoogle Scholar
  166. 166.
    Wu, J. X., Maes, L., Andries, R., Warson, F., Gepts, W., and Bourgain, R. H., 1985, Early morphologic changes in coronary arteries of experimental diabetic rats, Acta Diabetol. Lat. 22:317–326.PubMedGoogle Scholar
  167. 167.
    Dolgov, V. V., Zaikina, O. E., Bondarenko, M. F., and Repin, V. S., 1982, Aortic endothelium of alloxan diabetic rabbits: A quantitative study using scanning electron microscopy, Diabetologia 22:338–343.PubMedGoogle Scholar
  168. 168.
    Malik, R. A., Newrick, P. G., Sharma, A. K., Jennings, A., Ah-See, A. K., Mayhew, T. M., Jakubowski, J., Boulton, A. J., and Ward, J. D., 1989, Microangiopathy in human diabetic neuropathy: Relationship between capillary abnormalities and the severity of neuropathy, Diabetologia 32:92–102.PubMedGoogle Scholar
  169. 169.
    Powell, H. C., and Myers, R. R., 1984, Axonopathy and microangiopathy in chronic alloxan diabetes, Acta Neuropathol. 65:128–137.PubMedGoogle Scholar
  170. 170.
    Dyck, P. J., Hansen, S., Karnes, J., O’Brien, P., Yasuda, H., Windeband, A., and Zimmerman, B., 1985, Capillary number and percentage closed in human diabetic sural nerve, Proc. Natl. Acad. Sci. USA 82:2513–2517.PubMedGoogle Scholar
  171. 171.
    Powell, H. C., Rosoff, J., and Myers, R. R., 1985, Microangiopathy in human diabetic neuropathy, Acta Neuropathol. 68:295–305.PubMedGoogle Scholar
  172. 172.
    Vracko, R., 1982, A comparison of the microvascular lesions in diabetes mellitus with those in normal aging, Am. Geriatr. Soc. 30:201–205.Google Scholar
  173. 173.
    Agren, A., Rehn, G., and Naeser, P., 1979, Morphology and enzyme activities of the retinal capillaries in streptozotocin-diabetic mice, Acta Ophthalmol. 57:1065–1069.Google Scholar
  174. 174.
    Naeser, P., and Agren, A., 1978, Morphology and enzyme activities of the retinal capillaries in mice with the obese-hyperglycemic syndrome (gene symbol OB), Acta Ophthalmol. 56:607–616.Google Scholar
  175. 175.
    Toop, M. J., Dallinger, K. J. C., Jennings, P. E., and Barnett, A. H., 1986, Angiotensin-Converting enzyme (ACE): Relationship to insulin-dependent diabetes and microangiopathy, Diabetic Med. 3:455–457.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1992

Authors and Affiliations

  • Robert S. Bar
    • 1
  1. 1.Diabetes and Endocrinology Research CenterUniversity of IowaIowa CityUSA

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