Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Dec 15;89(24):11716–11720. doi: 10.1073/pnas.89.24.11716

Insulin-like growth factor II stimulates motor nerve regeneration.

S L Near 1, L R Whalen 1, J A Miller 1, D N Ishii 1
PMCID: PMC50627  PMID: 1465388

Abstract

Injury to mammalian motor nerves can lead to paralysis, but relatively successful regeneration may occur when conditions are favorable. Elucidation of the mechanism upholding successful regeneration is of theoretical and clinical interest. In this study, the hypothesis that insulin-like growth factor II (IGF-II) can stimulate motor nerve regeneration was tested. When IGF-II was infused continuously near a site of crush on the sciatic nerve, the distance of motor axon regeneration was increased significantly in rats. In contrast, spontaneous regeneration was inhibited when an anti-IGF-II antiserum was infused through a "window" in the epineurium. Thus, infused IGF-II can increase, and endogenous IGFs can support, the regeneration of motor axons in lesioned nerves.

Full text

PDF
11716

Images in this article

11717Image
on p.11717
11718Image
on p.11718

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bisby M. A., Chen S. Delayed wallerian degeneration in sciatic nerves of C57BL/Ola mice is associated with impaired regeneration of sensory axons. Brain Res. 1990 Oct 15;530(1):117–120. doi: 10.1016/0006-8993(90)90666-y. [DOI] [PubMed] [Google Scholar]
  2. Bohannon N. J., Corp E. S., Wilcox B. J., Figlewicz D. P., Dorsa D. M., Baskin D. G. Localization of binding sites for insulin-like growth factor-I (IGF-I) in the rat brain by quantitative autoradiography. Brain Res. 1988 Mar 22;444(2):205–213. doi: 10.1016/0006-8993(88)90931-6. [DOI] [PubMed] [Google Scholar]
  3. Bresjanac M., Sketelj J. Neurite-promoting influences of proliferating Schwann cells and target-tissues are not prerequisite for rapid axonal elongation after nerve crush. J Neurosci Res. 1989 Dec;24(4):501–507. doi: 10.1002/jnr.490240407. [DOI] [PubMed] [Google Scholar]
  4. Caroni P., Grandes P. Nerve sprouting in innervated adult skeletal muscle induced by exposure to elevated levels of insulin-like growth factors. J Cell Biol. 1990 Apr;110(4):1307–1317. doi: 10.1083/jcb.110.4.1307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Carsten R. E., Whalen L. R., Ishii D. N. Impairment of spinal cord conduction velocity in diabetic rats. Diabetes. 1989 Jun;38(6):730–736. doi: 10.2337/diab.38.6.730. [DOI] [PubMed] [Google Scholar]
  6. De Koning P., Brakkee J. H., Gispen W. H. Methods for producing a reproducible crush in the sciatic and tibial nerve of the rat and rapid and precise testing of return of sensory function. Beneficial effects of melanocortins. J Neurol Sci. 1986 Jul;74(2-3):237–246. doi: 10.1016/0022-510x(86)90109-7. [DOI] [PubMed] [Google Scholar]
  7. Easter S. S., Jr, Purves D., Rakic P., Spitzer N. C. The changing view of neural specificity. Science. 1985 Nov 1;230(4725):507–511. doi: 10.1126/science.4048944. [DOI] [PubMed] [Google Scholar]
  8. Frykman G. K., McMillan P. J., Yegge S. A review of experimental methods measuring peripheral nerve regeneration in animals. Orthop Clin North Am. 1988 Jan;19(1):209–219. [PubMed] [Google Scholar]
  9. GUTH L. Regeneration in the mammalian peripheral nervous system. Physiol Rev. 1956 Oct;36(4):441–478. doi: 10.1152/physrev.1956.36.4.441. [DOI] [PubMed] [Google Scholar]
  10. Hansson H. A., Dahlin L. B., Danielsen N., Fryklund L., Nachemson A. K., Polleryd P., Rozell B., Skottner A., Stemme S., Lundborg G. Evidence indicating trophic importance of IGF-I in regenerating peripheral nerves. Acta Physiol Scand. 1986 Apr;126(4):609–614. doi: 10.1111/j.1748-1716.1986.tb07862.x. [DOI] [PubMed] [Google Scholar]
  11. Hardouin S., Hossenlopp P., Segovia B., Seurin D., Portolan G., Lassarre C., Binoux M. Heterogeneity of insulin-like growth factor binding proteins and relationships between structure and affinity. 1. Circulating forms in man. Eur J Biochem. 1987 Dec 30;170(1-2):121–132. doi: 10.1111/j.1432-1033.1987.tb13676.x. [DOI] [PubMed] [Google Scholar]
  12. Haselbacher G., Humbel R. Evidence for two species of insulin-like growth factor II (IGF II and "big" IGF II) in human spinal fluid. Endocrinology. 1982 May;110(5):1822–1824. doi: 10.1210/endo-110-5-1822. [DOI] [PubMed] [Google Scholar]
  13. Hossenlopp P., Seurin D., Segovia-Quinson B., Binoux M. Identification of an insulin-like growth factor-binding protein in human cerebrospinal fluid with a selective affinity for IGF-II. FEBS Lett. 1986 Nov 24;208(2):439–444. doi: 10.1016/0014-5793(86)81065-1. [DOI] [PubMed] [Google Scholar]
  14. Hsu S. M., Raine L., Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577–580. doi: 10.1177/29.4.6166661. [DOI] [PubMed] [Google Scholar]
  15. Ide C., Tohyama K., Yokota R., Nitatori T., Onodera S. Schwann cell basal lamina and nerve regeneration. Brain Res. 1983 Dec 12;288(1-2):61–75. doi: 10.1016/0006-8993(83)90081-1. [DOI] [PubMed] [Google Scholar]
  16. Ishii D. N. Relationship of insulin-like growth factor II gene expression in muscle to synaptogenesis. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2898–2902. doi: 10.1073/pnas.86.8.2898. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kanje M., Skottner A., Lundborg G., Sjöberg J. Does insulin-like growth factor I (IGF-1) trigger the cell body reaction in the rat sciatic nerve? Brain Res. 1991 Nov 1;563(1-2):285–287. doi: 10.1016/0006-8993(91)91547-e. [DOI] [PubMed] [Google Scholar]
  18. Kanje M., Skottner A., Sjöberg J., Lundborg G. Insulin-like growth factor I (IGF-I) stimulates regeneration of the rat sciatic nerve. Brain Res. 1989 May 8;486(2):396–398. doi: 10.1016/0006-8993(89)90531-3. [DOI] [PubMed] [Google Scholar]
  19. Lesniak M. A., Hill J. M., Kiess W., Rojeski M., Pert C. B., Roth J. Receptors for insulin-like growth factors I and II: autoradiographic localization in rat brain and comparison to receptors for insulin. Endocrinology. 1988 Oct;123(4):2089–2099. doi: 10.1210/endo-123-4-2089. [DOI] [PubMed] [Google Scholar]
  20. Longo F. M., Hayman E. G., Davis G. E., Ruoslahti E., Engvall E., Manthorpe M., Varon S. Neurite-promoting factors and extracellular matrix components accumulating in vivo within nerve regeneration chambers. Brain Res. 1984 Aug 20;309(1):105–117. doi: 10.1016/0006-8993(84)91014-x. [DOI] [PubMed] [Google Scholar]
  21. Lundborg G., Dahlin L. B., Danielsen N., Gelberman R. H., Longo F. M., Powell H. C., Varon S. Nerve regeneration in silicone chambers: influence of gap length and of distal stump components. Exp Neurol. 1982 May;76(2):361–375. doi: 10.1016/0014-4886(82)90215-1. [DOI] [PubMed] [Google Scholar]
  22. Lunn E. R., Perry V. H., Brown M. C., Rosen H., Gordon S. Absence of Wallerian Degeneration does not Hinder Regeneration in Peripheral Nerve. Eur J Neurosci. 1989;1(1):27–33. doi: 10.1111/j.1460-9568.1989.tb00771.x. [DOI] [PubMed] [Google Scholar]
  23. Marquardt H., Todaro G. J., Henderson L. E., Oroszlan S. Purification and primary structure of a polypeptide with multiplication-stimulating activity from rat liver cell cultures. Homology with human insulin-like growth factor II. J Biol Chem. 1981 Jul 10;256(13):6859–6865. [PubMed] [Google Scholar]
  24. Mill J. F., Chao M. V., Ishii D. N. Insulin, insulin-like growth factor II, and nerve growth factor effects on tubulin mRNA levels and neurite formation. Proc Natl Acad Sci U S A. 1985 Oct;82(20):7126–7130. doi: 10.1073/pnas.82.20.7126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Nachemson A. K., Lundborg G., Hansson H. A. Insulin-like growth factor I promotes nerve regeneration: an experimental study on rat sciatic nerve. Growth Factors. 1990;3(4):309–314. doi: 10.3109/08977199009003673. [DOI] [PubMed] [Google Scholar]
  26. Neumann D., Scherson T., Ginzburg I., Littauer U. Z., Schwartz M. Regulation of mRNA levels for microtubule proteins during nerve regeneration. FEBS Lett. 1983 Oct 17;162(2):270–276. doi: 10.1016/0014-5793(83)80770-4. [DOI] [PubMed] [Google Scholar]
  27. Pearson R. C., Taylor N., Snyder S. H. Tubulin messenger RNA: in situ hybridization reveals bilateral increases in hypoglossal and facial nuclei following nerve transection. Brain Res. 1988 Nov 1;463(2):245–249. doi: 10.1016/0006-8993(88)90396-4. [DOI] [PubMed] [Google Scholar]
  28. Politis M. J., Ederle K., Spencer P. S. Tropism in nerve regeneration in vivo. Attraction of regenerating axons by diffusible factors derived from cells in distal nerve stumps of transected peripheral nerves. Brain Res. 1982 Dec 16;253(1-2):1–12. doi: 10.1016/0006-8993(82)90667-9. [DOI] [PubMed] [Google Scholar]
  29. Recio-Pinto E., Ishii D. N. Effects of insulin, insulin-like growth factor-II and nerve growth factor on neurite outgrowth in cultured human neuroblastoma cells. Brain Res. 1984 Jun 8;302(2):323–334. doi: 10.1016/0006-8993(84)90246-4. [DOI] [PubMed] [Google Scholar]
  30. Recio-Pinto E., Ishii D. N. Insulin and insulinlike growth factor receptors regulating neurite formation in cultured human neuroblastoma cells. J Neurosci Res. 1988 Mar;19(3):312–320. doi: 10.1002/jnr.490190306. [DOI] [PubMed] [Google Scholar]
  31. Recio-Pinto E., Rechler M. M., Ishii D. N. Effects of insulin, insulin-like growth factor-II, and nerve growth factor on neurite formation and survival in cultured sympathetic and sensory neurons. J Neurosci. 1986 May;6(5):1211–1219. doi: 10.1523/JNEUROSCI.06-05-01211.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Rinderknecht E., Humbel R. E. Primary structure of human insulin-like growth factor II. FEBS Lett. 1978 May 15;89(2):283–286. doi: 10.1016/0014-5793(78)80237-3. [DOI] [PubMed] [Google Scholar]
  33. Rotwein P., Burgess S. K., Milbrandt J. D., Krause J. E. Differential expression of insulin-like growth factor genes in rat central nervous system. Proc Natl Acad Sci U S A. 1988 Jan;85(1):265–269. doi: 10.1073/pnas.85.1.265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Sara V. R., Carlsson-Skwirut C. The role of the insulin-like growth factors in the regulation of brain development. Prog Brain Res. 1988;73:87–99. doi: 10.1016/S0079-6123(08)60499-9. [DOI] [PubMed] [Google Scholar]
  35. Seitz R. J., Reiners K., Himmelmann F., Heininger K., Hartung H. P., Toyka K. V. The blood-nerve barrier in Wallerian degeneration: a sequential long-term study. Muscle Nerve. 1989 Aug;12(8):627–635. doi: 10.1002/mus.880120803. [DOI] [PubMed] [Google Scholar]
  36. Sjöberg J., Kanje M. Insulin-like growth factor (IGF-1) as a stimulator of regeneration in the freeze-injured rat sciatic nerve. Brain Res. 1989 Apr 17;485(1):102–108. doi: 10.1016/0006-8993(89)90671-9. [DOI] [PubMed] [Google Scholar]
  37. Smith M., Clemens J., Kerchner G. A., Mendelsohn L. G. The insulin-like growth factor-II (IGF-II) receptor of rat brain: regional distribution visualized by autoradiography. Brain Res. 1988 Apr 5;445(2):241–246. doi: 10.1016/0006-8993(88)91185-7. [DOI] [PubMed] [Google Scholar]
  38. Soares M. B., Ishii D. N., Efstratiadis A. Developmental and tissue-specific expression of a family of transcripts related to rat insulin-like growth factor II mRNA. Nucleic Acids Res. 1985 Feb 25;13(4):1119–1134. doi: 10.1093/nar/13.4.1119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Soares M. B., Turken A., Ishii D., Mills L., Episkopou V., Cotter S., Zeitlin S., Efstratiadis A. Rat insulin-like growth factor II gene. A single gene with two promoters expressing a multitranscript family. J Mol Biol. 1986 Dec 20;192(4):737–752. doi: 10.1016/0022-2836(86)90025-2. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES