Skip to main content
SpringerLink
Log in

Cellular mechanisms underlying the development of diabetic neuropathies

  • Reviews
  • Published:
Neurophysiology Aims and scope

Abstract

The data of recent studies of fundamental mechanisms underlying the development of diabetic neuropathies are summarized in the Review. The importance of a sorbitol-polyol pathway of glucose metabolism, as well as the roles of production of peroxide radicals and activation of the processes of non-enzymatic glycosilation in the nerve cells are analyzed. Special attention is paid to the roles of growth factors in morphological modifications of the neuronal structures and to that of intracellular signalization in functional disturbances in the nerve cells. Changes in intracellular homeostasis of Ca ions are of considrable importance for the development of peripheral diabetic neuropathies.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. M. I. Balabolkin,Diabetes Mellitus [in Russian], Meditsina, Moscow (1994).

    Google Scholar 

  2. J. Pirart, “Diabetes mellitus and its degenerative complications: a prospective study of 4,400 patients observed between 1947 and 1973,”Diabetes Care,1, 168–188 (1978).

    Google Scholar 

  3. A. J. Vinik, F. J. Linzze, M. T. Holland, et al., “Diabetic neuropathies,”Diabetes Care,15, 1926–1975 (1992).

    PubMed  CAS  Google Scholar 

  4. A. A. F. Sima, P. K. Thomas, D. Ishii, et al., “Diabetic neuropathy,”Diabetologia,40, B74-B77 (1997).

    Article  PubMed  Google Scholar 

  5. D. A. Green, A. A. F. Sima, J. W. Albers, et al., “Diabetic neuropathy,” in:Diabetes Mellitus, Theory and Practice, H. Rifkin and D. Portae (eds.), Elsevier, New York, Amsterdam, London (1993), pp. 710–756.

    Google Scholar 

  6. P. J. Oates, “The polyol pathway—a culprit in diabetic neuropathy?,”Neurosci. Res. Commun.,21, No. 1, 33–40 (1997).

    Article  Google Scholar 

  7. G. Said, C. Goulon-Gonan, G. Slama, et al., “Severe earlyonset polyneuropathy in insulin-dependentdiabetes mellitus: a clinical and pathological study,”New Eng. J. Med.,26, 1257–1263 (1992).

    Article  Google Scholar 

  8. A. A. F. Sima, V. Nathaniel, V. Bril, et al., “Histopathological heterogeneity of neuropathy in insulin-dependent and non-insulin-dependent diabetes and demonstration of axo-glial dysjunction in human diabetic neuropathy,”J. Clin. Invest.,81, 349–364 (1988).

    PubMed  CAS  Google Scholar 

  9. D. D. Sandeman, A. C. Shore, and Y. E. Tooke, “Relation of skin capillary pressure in patients with insulin-dependentdiabetes mellitus to complications and metabolic control,”new Eng. J. Med.,327 760–764 (1992).

    Article  PubMed  CAS  Google Scholar 

  10. A. C. Shore, A. J. Jaap and J. E. Tooke, “Capillary pressure in patients with NIIDM,”Diabetes,43, 1198–1202 (1994).

    PubMed  CAS  Google Scholar 

  11. A. A. F. Sima, W.-X. Zhang, W. J. Tze, et al., “Diabetic neuropathy in induced diabetic rat and effect of allogenic islet transplantation: morphometric analysis,”Diabetes,37, 1129–1136 (1988).

    PubMed  CAS  Google Scholar 

  12. P. Sidenius and J. Jacobsen, “Reversibility and preventability of the decrease in slow axonal transport velocity in experimental diabetes,”Diabetes,31, 689–693 (1982).

    PubMed  CAS  Google Scholar 

  13. Y. R. Larsen and P. Sidenius, “Slow axonal transport of structural polypeptides in rat, early changes in streptozotocin diabetes and effect of insulin treatment,”J. Neurochem,52, 390–401 (1989).

    PubMed  CAS  Google Scholar 

  14. R. Watanabe, “Molecular biological study on pathogenesis of diabetic neuropathy: alterations in mRNA expression of aldose reductase and axonal cytoskeletal protein,”Hirosaki Med. J.,45, S196-S204 (1993).

    CAS  Google Scholar 

  15. P. K. Thomas, D. W. Wright, and E. Tzebelikos, “Amino acid uptake by dorsal root ganglia from STZ-diabetic rats,”J. Neurol. Neurosurg. Psychiat.,47, 912–916 (1984).

    PubMed  CAS  Google Scholar 

  16. V. J. Brewster, L. T. Diemel, L. Mohiuddin, and D. R. Tomlinson, “Diabetic neuropathy, nerve growth factor and other neurotrophic factors,”TINS,17, No. 8, 321–325 (1994).

    PubMed  CAS  Google Scholar 

  17. V. Faradji and J. Sotelo, “Low serum levels of nerve growth factor in diabetes neuropathy,”Acta Neurol. Scand.,81, 402–406 (1990).

    Article  PubMed  CAS  Google Scholar 

  18. S. Yagihashi, “Pathology and pathogenetic mechanisms of diabetic neuropathy,”Diabetes/Met. Rev.,11, No. 3, 193–225 (1995).

    Article  CAS  Google Scholar 

  19. O. Kasayama and T. Oka, “Impaired production of nerve growth factor in the submandibular gland of diabetic mice,”Am. J. Physiol.,257, E400-E404 (1989).

    PubMed  CAS  Google Scholar 

  20. M. J. Stevens, E. L. Feldman, and D. A. Greene, “The aetiology of diabetic neuropathy: the combined roles of metabolic and vascular defects,”Diabetic Med.,12, 566–579 (1995).

    PubMed  CAS  Google Scholar 

  21. P. Kostyuk and A. Verkhratsky,Calcium Signalling in the Nervous System, Wiley and Sons, Chichester, New York, Brisbane, Toronto, Singapore (1995).

    Google Scholar 

  22. L. J. Sake and A. F. Eakes, “Epidermal growth factor stimulates the production of phosphatidylinositol monophosphate and the breakdown of polyphosphoinostides in A431 cells,”J. Biol. Chem.,262, 1644–1651 (1987).

    Google Scholar 

  23. S. A. Rogers and M. R. Hammerman, “Insulin-like growth factor II stimulates production of inositoltrisphosphate in proximal tubular basolateral membrane from canine kidney,”Proc. Natl. Acad. Sci. USA,85, 4037–4041 (1988).

    Article  PubMed  CAS  Google Scholar 

  24. R. M. Lindsay and M. Harmar, “Nerve growth factor regulates expression of neuropeptide's genes in adult sensory neurons,”Nature,337, 362–364 (1989).

    Article  PubMed  CAS  Google Scholar 

  25. R. M. Lindsay, C. Locket, J. Stenberg, et al., “Neuropeptide expression in cultures of adult sensory neurons; modulation of substance P and calcitonin-gene-related peptide levels by nerve growth factors,”Neuroscience,33, 53–65 (1989).

    Article  PubMed  CAS  Google Scholar 

  26. L. T. Diemel P. Fernyhough, K. Maeda, et al., “Nerve growth factor (NGF) treatment normalizes NGF and neuropeptides in sciatic nerve of streptozotocin-diabetic rats without affecting motor nerve conduction or nerve laser-Doppler flux,” in:Diabetic Neuropathy, New Concepts and Insights, N. Hotta, D. Greene, J. D. Ward, et al. (eds.), International Congress Sereis 1084, Excerpta Medica, Elsevier, Amsterdam, Lausanne, New York, Oxford, Shannon, Tokyo (1995), pp. 169–173.

    Google Scholar 

  27. S. M. Grain, “Neurotrophic factors in diabetic neuropathy,”TINS,18, No. 1, 15–16 (1995).

    Google Scholar 

  28. J. W. Griffin, R. Goerge, C. Lobata, et al., “Macrophage response and myelin clearance during Wallerian degeneration: relevance to immune mediated demyelinization,”J. Neuroimmunol.,40, 153–166 (1992).

    Article  PubMed  CAS  Google Scholar 

  29. V. H. Perry and M. C. Brown, “Role of macrophages in peripheran nerve degeneration and repair,”BioEssays,14, 401–406 (1992).

    Article  PubMed  CAS  Google Scholar 

  30. A. A. F. Sima, J. Levitan, H. Ristic, et al., “Nerve fiber regeneration in the spontaneously diabetic BB/W rat,” in:Diabetic Neuropathy, New Concepts and Insights N. Hotta, D. A. Greene, J. D. Ward, et al. (eds.), International Congress Series 1084, Excerpta Medica, Elsevier, Amsterdam, Lausanne, New York, Oxford, Shannon, Tokyo (1995), pp. 27–36.

    Google Scholar 

  31. C. L. Crawford and M. J. Hobbs, “Neurotrophic factors in diabetic neuropathy,”TINS,18, No. 1, 15 (1995).

    PubMed  CAS  Google Scholar 

  32. D. A. Green, S. A. Lattimer, and A. A. F. Sima, “Tissue-specific metabolic alterations in the pathogenesis of diabetic peripheral neuropathy,” in:Tissue Specific Alterations in Diabetes, F. Belfore, G. M. Mollinatti, and G. U. Reaven (eds.), Karger, Basel (1990).

    Google Scholar 

  33. T. C. Hohman and H. M. Kwon, “Two separate mechanisms for the glucose inhibition of myoinositol transport,” in:Diabetic Neuropathy, New Concepts and Insights, N. Hotta, D. Greene, J. D. Ward, et al. (eds.), International Congress Series 1084, Excerpta Medica, Elsevier, Amsterdam, Lausanne, New York, Oxford, Shannon, Tokyo, (1995), pp. 43–58.

    Google Scholar 

  34. J. Kim, E. H. Rushovich, T. P. Thomas, et al., “Diminished specific activity of cytosolic protein kinase C in sciatic nerve of streptozotocin-diabetic rats and its correction by dietary myo-inositol,”Diabetes,40, 1545–1554 (1991).

    PubMed  CAS  Google Scholar 

  35. D. A. Greene, S. A. Latimer, and A. A. F. Sima, “Are disturbances of sorbitol phosphoinositide and Na+/K+-ATPase regulation involved in pathogenesis of diabetic neuropathy?,”Diabetes,37, 688–693 (1988).

    PubMed  CAS  Google Scholar 

  36. R. P. Rubin,Calcium and Cellular Secretion, Plenum Press, New York, London (1982).

    Google Scholar 

  37. C. D. Ferris, and S. H. Snyder, “Inositol phosphate receptors and calcium disposition in the brain,”J. Neurosci.,12, 1567–1574 (1992).

    PubMed  CAS  Google Scholar 

  38. T. Inogushi, R. Battan, E. Handler, et al., “Preferential elevation of protein kinase C isoform βII and dicylglycerol levels in the aorta and heart of diabetic rats,”Proc. Natl. Acad. Sci. USA,89, 11059–11063 (1992).

    Article  Google Scholar 

  39. H. Ishii, M. R. Jirousek, D. Koya, et al., “Amelioration of vascular dysfunction in diabetic rats by an oral PKC B inhibitions,”Science,272, 728–731 (1996).

    PubMed  CAS  Google Scholar 

  40. T. Y. Goraya, P. Wilkins, and J. G. Douglas, “Signal transduction alterations in peripheral nerves from streptozotocin-induced diabetic rats,”J. Neurosci.,41, 518–525 (1995).

    Article  CAS  Google Scholar 

  41. N. E. Cameron and M. A. Cotter, “Mechanisms underlying impaired peripheral nerve perfusion and endoneural oxygenation in experimental diabetes: potential treatment strategies,” in:Diabetic Neuropathy, New Concepts and Insights, N. Hotta, D. Greene, J. D. Ward, et al. (eds.), International Congress Series 1084, Excerpta Medica, Elsevier, Amsterdam, Lausanne, New York, Oxford, Shannon, Tokyo (1995), pp. 3–15.

    Google Scholar 

  42. A. W. Norman and G. Litwack,Hormones, Acad. Press, San-Diego, London, Boston, New York, Sydney, Tokyo, Toronto (1997).

    Google Scholar 

  43. M. J. Stevens, “Nitric oxide as a potential bridge between the metabolic and vascular hypothesis of diabetic neuropathy,”Diabetic Med.,12, 292–295 (1995).

    Article  PubMed  CAS  Google Scholar 

  44. L. Sobrevia and G. E. Mann, “Dysfunction of the endothelial nitric oxide signalling pathway in diabetes and hyperglycemia,”Exp. Phsyiol.,82, 423–452 (1997).

    CAS  Google Scholar 

  45. A. Zahadnikova and O. Krizanova, “Nitric oxide and its effects on the calcium transport system in the myocardium,”J. Physiol. Biophys.,16, 197–215 (1997).

    Google Scholar 

  46. M. Nakane, L. Mitchel, U. Forstermann, et al., “Phosphorylation by calcium/calmodulin-dependent protein kinase II and protein kinase C the activity of nitric oxide synthase,”Biochem. Biophys. Res. Commun,180, 1396–1402 (1991).

    Article  PubMed  CAS  Google Scholar 

  47. K. S. Murthy, J. G. Jim, and G. M. Makhlouf, “Inhibition of nitric oxide synthase activity in dispersed gastric muscle cells by protein kinase C,”Am. J. Physiol.,266, No. 29, G161-G165 (1994).

    PubMed  CAS  Google Scholar 

  48. D. A. Greene and M. J. Stevens, “Interaction of metabolic and vascular factors in the pathogenesis of diabetic neuropathy,” in:Diabetic Neuropathy, New Concepts and Insights, N. Hotta, D. Greene, J. D. Ward, et al. (eds.), International Congress Series, 1084, Excerpta Medica, Elsevier, Amsterdam, Lausanne, New York, Oxford, Shannon, Tokyo (1995), pp. 37–43.

    Google Scholar 

  49. P. A. Low, “Recent studies on experimental diabetic neuropathy,” in:Diabetic Neuropathy, New Concepts and Insights, N. Hotta, D. Greene, J. D. Ward, et al. (eds.) International Congress Series 1084, Excerpta Medica, Elsevier, Amsterdam, Lausanne, New York, Oxford, Shannon, Tokyo (1995), pp. 17–23.

    Google Scholar 

  50. T. Ohkuwa, Y. Sato, and M. Naoi, “Hydroxyl radical formation in diabetic rats induced by streptozotocin,”Life Sci. 56, No. 21, 1789–1798 (1995).

    Article  PubMed  CAS  Google Scholar 

  51. M. Gavella, “Oxidative stress and role of antioxidants in male infertility,”Diabetologia Croatica,26, No. 2, 65–68 (1997).

    Google Scholar 

  52. B. S. Krystal, C. T. Jackson, and H. Y. Chung, “Defects at center P underlie diabetes-associated mitochondrial dysfunction,”Free Rad. Med.,22, No. 5, 823–833 (1997).

    Article  Google Scholar 

  53. M. Brownlee, “Advanced products of nonenzymatic glycosylation and the pathogenesis of diabetic complications,” in:Diabetes Mellitus, Theory and Practice, H. Rifkin and D. Portae (eds.), Elsevier, New York, Amsterdam, London (1993), pp. 279–292.

    Google Scholar 

  54. S. Yagihashi, M. Kamijo, Y. Ido, et al., “Effects of long-term aldose reductase inhibition on development of experimental diabetic neuropathy: ultrastructural and morphometric studies on sural nerve in streptozotocin-induced diabetic rats,”Diabetes,39, 690–696 (1990).

    PubMed  CAS  Google Scholar 

  55. N. A. Cullum, J. Mahon, K. Stringer, et al., “Glycation of rat sciatic nerve tubulin in experimentaldiabetes mellitus, “Diabetologia,43, 387–389 (1991).

    Article  Google Scholar 

  56. M. Cohen,Diabetes Glycosylation Measurement and Biologic relevance, Springer-Verlag, New York, Berlin, Heiderberg, Tokyo (1986).

    Google Scholar 

  57. K. Sugimoto and S. Yagihashi, “In situ localization of early and advanced glycation products in the peripheral nerve of streptozotocin diabetic rats,”Diabetes,44, Suppl. 1, 11A (1995).

    Google Scholar 

  58. G. Biessels and W. H. Gispen, “The calcium hypothesis of brain aging and neurodegenarative disorders: significance in diabetic neuropathy,”Life Sci.,59, 379–387 (1996).

    Article  PubMed  CAS  Google Scholar 

  59. E. Carstens, “Neural mechanisms of hyperalgesia: peripheral or central sensitization?”,NIPS,10, 260–265 (1995).

    Google Scholar 

  60. E. Kostyuk, N. Pronchuk, and A. Shmigol, “Calcium signal prolongation in sensory neurones of mice with experimental diabetes,”neuroReport,6, 1010–1012 (1994).

    Article  Google Scholar 

  61. K. E. Hall, A. A. F. Sima, and J. W. Wiley, “Voltage-dependent calcium currents are enchanced in dorsal root ganglion neurones from the Bio/Bred/Worchester diabetic rat,”J. Physiol.,486, No. 2, 313–322 (1995).

    PubMed  CAS  Google Scholar 

  62. K. E. Hall, A. A. F. Sima, and J. W. Wiley, “Opiate-mediated inhibition of calcium signalling is decreased in dorsal root ganglion neurons from diabetic BB/W rat,”J. Clin. Invest.,97, No. 5, 1165–1172 (1996).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Endocrinology and Metabolism, Academy of Medical Sciences of Ukraine, Kyiv, Ukraine

    E. P. Kostyuk

Authors
  1. E. P. Kostyuk
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kostyuk, E.P. Cellular mechanisms underlying the development of diabetic neuropathies. Neurophysiology 30, 120–127 (1998). https://doi.org/10.1007/BF02463061

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02463061

Keywords

Search

Navigation