Skip to main content
Log in

ACTH4–9 analogue ORG 2766 can improve existing neuropathy in streptozocin-induced diabetic rats

  • Originals
  • Published:
Acta Diabetologica Aims and scope Submit manuscript

Abstract

The effect of treatment of an existing neuropathy in streptozocin-induced diabetic rats with the ACTH4–9 analogue ORG 2766 was examined. Four groups of rats were studied: group 1 consisted of age-matched, non-diabetic controls and groups 2, 3 and 4 of diabetic rats. Sensory and motor nerve conduction velocity (SNCV and MNCV) were measured at weeks 0, 4, 6, 8 and 10. Four weeks after the administration of streptozocin (STZ) all diabetic rats showed a significant slowing of SNCV and MNCV. Treatment was then started: group 2 was treated with placebo, group 3 with a low dos (1 μg) of ACTH4–9 subcutaneously every 48h, and group 4 with a high dos (10 μg) of ACTH4–9 subcutaneously every 48 h. The animals treated with the high peptide dosage showed a significant improvement in both SNCV and MNCV from week 6 onwards, whereas this beneficial effect was not demonstrated for the rats treated with the low dosage. This study demonstrates that the ACTH4–9 analogue ORG 2766 can ameliorate existing diabetic neuropathy in STZ-induced diabetic rats.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Greene DA, DeJesus PV Jr, Winegrad AI, Effects of insulin and dietary myoinositol on impaired peripheral motor nerve conduction velocity in acute streptozotocin diabetes. J Clin Invest 55:1326–1336, 1975

    Google Scholar 

  2. Sima AAF, Zhang WX, Tze WJ, Tai J, Nathaniel V, Diabetic neuropathy in STZ-induced diabetic rats and effect of allogeneic islet cell transplantation. Diabetes 37:1129–1136, 1988

    Google Scholar 

  3. Greene DA, Lattimer DA, Impaired rat sciatic nerve sodium-potassium ATPase activity in acute streptozocin diabetes and its correction by dietary myo-inositol supplementation. J Clin Invest 72:1058–1063, 1983

    Google Scholar 

  4. Finegold D, Lattimer SA, Nolle S, Bernstein M, Greene DA, Polyol pathway activity and myo-inositol metabolism: a suggested relationship in pathogenesis of diabetic neuropathy. Diabetes 32:988–992, 1983

    Google Scholar 

  5. Tuck RR, Schmelzer JD, Low PA, Endoneurial blood flow and oxygen tension in sciatic nerves of rats with experimental diabetic neuropathy. Brain 107:935–950, 1984

    Google Scholar 

  6. Low PA, Tuck RR, Dyck PJ, Schmelzer JD, Yao JK, Prevention of some electrophysiologic and biochemical abnormalities with oxygen supplementation in experimental diabetic neuropathy. Proc Natl Acad Sci USA 81:6894–6898, 1984

    Google Scholar 

  7. Low PA, Schmelzer JD, Ward KK, Yao JK, Experimental chronic hypoxic neuropathy: relevance to diabetic neuropathy. Am J Physiol 250:E94–99, 1986

    Google Scholar 

  8. Low PA, Nickander KK, Oxygen free radical effects in sciatic nerve in experimental diabetes. Diabetes 40:873–877, 1991

    Google Scholar 

  9. Vlassara H, Brownlee M, Cerami A, Excessive non-enzymatic glycosylation of peripheral and central nervous system myelin components in diabetic rats. Diabetes 32:670–674, 1983

    Google Scholar 

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

    Google Scholar 

  11. Tomlinson DR, Moriarty RJ, Mayer JH, Prevention and reversal of defective axonal transport and motor nerve conduction velocity in rats with experimental diabetes by treatment with the aldose reductase inhibitor sorbinil. Diabetes 33:470–476, 1984

    Google Scholar 

  12. De Koning P, Neijt JP, Jennekens FGI, Gispen WH, ORG 2766 protects from cisplatinin-induced neurotoxicity in rats. Exp Neurol 97:746–750, 1987

    Google Scholar 

  13. Gerritsen van der Hoop R, De Koning P, Boven E, Neijt JP, Jennekens FGI, Gispen WH, Efficacy of the neuropeptide ORG 2766 in the prevention and treatment of cis-platinin-induced neurotoxicity in rats. Eur J Cancer Clin Oncol 24:637–642, 1988

    Google Scholar 

  14. Gerritsen van der Hoop R, Vecht CJ, Van den Burg MEL, Haanstra W, Boogerd W, ten Bokkel Huinink W, Heijmans JJ, Vermorken J, Jennekens FGI, Van Houwelingen JC, Gispen WH, Neijt JP, Prevention of cisplatinin neurotoxicity with an ACTH(4–9) analogue in patients with ovarian cancer. N Engl J Med 322:89–94, 1990

    Google Scholar 

  15. Van der Zee CEEM, Gerritsen van der Hoop R, Gispen WH, Beneficial effect of Org 2766 in treatment of peripheral neuropathy in streptozotocin-induced diabetic rats. Diabetes 38:225–230, 1989

    Google Scholar 

  16. Bravenboer, Kappelle AC, Hamers FPT, Buren T van, Erkelens DW, Gispen WH, Potential use of glutathione for the prevention and treatment of diabetic neuropathy in the streptozotocin-induced diabetic rat. Diabetologia 35:813–817, 1992

    Google Scholar 

  17. Waxman SG, Determination of conduction velocity in myelinated nerve fibres. Muscle Nerve 3:141–150, 1980

    Google Scholar 

  18. Stanley EF, Sensory and motor nerve conduction velocities and the latency of the H-reflex during growth of the rat. Exp Neurol 71:497–506, 1981

    Google Scholar 

  19. Fleiss JL, The design and analysis of clinical experiments. Wiley, New York, 1986

    Google Scholar 

  20. Kim J, Kyriazi H, Greene DA, Normalization of Na+−K+-ATPase activity in isolated membrane fraction from sciatic nerves of streptozocin-induced diabetic rats by dietary myoinositol supplementation in vivo or protein kinase C agonists in vitro. Diabetes 40:558–567, 1991

    Google Scholar 

  21. Sonobe M, Yasuda H, Hisanaga T, Maeda K, Yamashita M, Kawabata T, Kikkawa R, Taiguchi Y, Shigeta Y, Amelioration of nerve Na+-analogue OP-1206. α-CD in streptozocin-induced diabetic rats. Diabetes 40:726–730, 1991

    Google Scholar 

  22. Gispen WH, Therapeutical potential for melanocortins in peripheral nerve disease. Trends Pharmacol Sci 11:221–222, 1990

    Google Scholar 

  23. De Koning P, Gispen WH, Org 2766 improves functional and electophysiological aspects of regenerating sciatic nerve in the rat. Peptides 8:415–422, 1987

    Google Scholar 

  24. De Koning P, Verhaagen J, Sloot W, Jennekens FGI, Gispen WH, ORG 2766 stimulated collateral sprouting in rat soleus muscle following partial denervation. Muscle Nerve 12:353–359, 1989

    Google Scholar 

  25. Bravenboer B, Kappelle AC, Buren T van, Erkelens DW, Gispen WH, ACTH4–9-analogue ORG 2766 improves existing diabetic neuropathy in theBB/Wor model. Diabetes 41 [Suppl 1]: A491, 1992

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bravenboer, B., Kappelle, A.C., van Buren, T. et al. ACTH4–9 analogue ORG 2766 can improve existing neuropathy in streptozocin-induced diabetic rats. Acta Diabetol 30, 21–24 (1993). https://doi.org/10.1007/BF00572869

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00572869

Key words

Navigation