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.
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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.
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.
Herbert V., Lau K. S., Gottlieb C. W., Bleicher S. J.: Coated charcoal immunoassay of insulin - J. clin. Endocr.25, 1375, 1965.
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.
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.
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.
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.
Orci L.: Personal communication.
Richardson B. P., McDaniel M. L., Lacy P. E.: Effects of cyproheptadine on insulin secretion by isolated perifused rat islets - Diabetes24, 836, 1975.
Santeusanio F., Faloona G. R., Unger R. H.: Suppressive effect of secretin upon pancreatic alpha cell function - J. clin. Invest.51, 1743, 1972.
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.
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.
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.
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.
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Kikkawa, R., Duvillard, D. & Stauffacher, W. The effects of cyproheptadine on glucose tolerance and pancreatic islets in rats. Acta diabet. lat 18, 107–114 (1981). https://doi.org/10.1007/BF02098995
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DOI: https://doi.org/10.1007/BF02098995