Advertisement

Acta diabetologia latina

, Volume 18, Issue 2, pp 107–114 | Cite as

The effects of cyproheptadine on glucose tolerance and pancreatic islets in rats

  • Ryuichi Kikkawa
  • Danielle Duvillard
  • Werner Stauffacher
Original Contributions

Summary

The effects of cyproheptadine (CPH) on plasma levels, of glucose, insulin and glucagon were studied in rats in order to clarify the diabetogenicity of this compound. CPH was given to the rats at a daily dose of 45 mg per kg body weight via gastric intubation for up to 20 days. Glucose intolerance appeared after 5 days of CPH treatment without significant increase in fasting glucose level. Plasma insulin response to glucose loading was depressed in the early phase of the glucose tolerance test in groups treated for 10 and 20 days. In these groups the insulinogenic index was significantly lowered. Pancreatic insulin content decreased rapidly after single dose of CPH. Plasma level and pancreatic content of glucagon were not changed by this compound. These results suggested that chronic treatment with CPH caused glucose intolerance in rats through its direct influence on pancreatic B-cell function.

Key-words

Cyproheptadine Diabetogenic compound Oral glucose tolerance test Pancreatic insulin and glucagon content 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1).
    Amherdt M., Humbert F., Rabinovitch A., Orci L., Renold A. E.: Alteration of insulinsecretory process by cyproheptadine: a correlative ultrastructural and biochemical study - 8th Congr. Int. Diabetes Fed., Bruxelles 1973; Excerpta Medica Amsterdam, 1973; p. 1, abstract≠1.Google Scholar
  2. 2).
    Drash A., Elliott J., Langs H., Lavenstein A. F., Cooke R. E.: The effect of cyproheptadine on carbohydrate metabolism - Clin. Pharmacol. Ther. 7, 340, 1966.PubMedGoogle Scholar
  3. 3).
    Herbert V., Lau K. S., Gottlieb C. W., Bleicher S. J.: Coated charcoal immunoassay of insulin - J. clin. Endocr.25, 1375, 1965.PubMedGoogle Scholar
  4. 4).
    Joost H. G., Beckmann J., Holze S., Lenzen S., Poster W., Hasselblatt A.: Inhibition of insulin and glucagon release from the perfused rat pancreas by cyproheptadine (Periactinol®, Nuran®)- Diabetologia12, 201, 1976.PubMedGoogle Scholar
  5. 5).
    Joost H. G., Beckmann J., Lenzen S., Hasselblatt A.: Inhibition of insulin release by cyproheptadine: effects on 3′,5′-cyclic-AMP-content and45Ca-accumulation of incubated mouse islets - Acta endocr. (Kbh.)82, 121, 1976.Google Scholar
  6. 6).
    Longnecker D. S., Wold J. S., Fischer L. J.: Ultrastructural study of alteration in beta cells of pancreatic islets from cyproheptadine-treated rats - Diabetes21, 71, 1971.Google Scholar
  7. 7).
    Malaisse W. J., Malaisse-Lagae F., King S.: Quantitative and qualitative aspects of islet function in the rat - J. Lab. clin. Med.71, 56, 1968.PubMedGoogle Scholar
  8. 8).
    Orci L.: Personal communication.Google Scholar
  9. 9).
    Richardson B. P., McDaniel M. L., Lacy P. E.: Effects of cyproheptadine on insulin secretion by isolated perifused rat islets - Diabetes24, 836, 1975.PubMedGoogle Scholar
  10. 10).
    Santeusanio F., Faloona G. R., Unger R. H.: Suppressive effect of secretin upon pancreatic alpha cell function - J. clin. Invest.51, 1743, 1972.PubMedGoogle Scholar
  11. 11).
    Seltzer H. S., Allen E. W., Herron A. L., Brennan M. T.: Insulin secretion in response to glycemic stimuli: relation of delayed initial release to carbohydrate intolerance in mild diabetes mellitus - J. clin. Invest.46, 323, 1967.PubMedGoogle Scholar
  12. 12).
    Volk B. W., Wellmann K. F.: Pathogenetic considerations on idiopathic diabetes - In:Volk B. W., Wellmann K. F. (Eds): The diabetic pancreas. Plenum Press, New York, 1977; p. 261.Google Scholar
  13. 13).
    Wold J. S., Fischer L. J.: The tissue distribution of cyproheptadine and its metabolites in rats and mice - J. Pharmacol. exp. Ther.183, 188, 1972.PubMedGoogle Scholar
  14. 14).
    Wold J. S., Longnecker D. S., Fischer L. J.: Species dependent pancreatic islet toxicity produced by cyproheptadine: alterations in beta cell structure and function - Toxicol. appl. Pharmacol.19, 188, 1977.Google Scholar

Copyright information

© Casa Editrice 1981

Authors and Affiliations

  • Ryuichi Kikkawa
    • 1
  • Danielle Duvillard
    • 1
  • Werner Stauffacher
    • 1
  1. 1.Medizinische Universitätsklinik Inselspital BernDeutschland

Personalised recommendations