Summary
40 mg/kg/day of cyproheptadine was given to groups of sham-operated and hypophysectomized young adult male rats by stomach tube for 10 days. Shamoperated and hypophysectomized control groups received vehicle only. In the sham-operated group cyproheptadine produced typical pancreatic B-cell vacuolization and degranulation, visible on light microscopy. Ultrastructural changes were mainly restricted to the rough endoplasmic reticulum where cysternal dilation, vesicle fusion and vacuole formation were common. The mean diameter of the islets of Langerhans was increased by 30%. Resting blood glucose levels were elevated significantly. No such findings were observed in the treated, hypophysectomized group of rats, indicating the importance of an intact pituitary for the genesis of these lesions and the accompanying hyperglycemia. The results also demonstrate that the effect of cyproheptadine on rat B-cells is not simply direct. The hypothesis that cyproheptadine may produce pancreatic B-cell changes through a drug-induced stimulation of pituitary or hypothalamic function is discussed.
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Stone, C.A., Wenger, H.C., Ludden, C.T., Stavorski, J.M., Ross, C.A.: Antiserotonin-antihistaminic properties of cyproheptadine. J. Pharmacol. exp. Ther.131, 73–84 (1961)
Noble, R.E.: Effect of cyproheptadine on appetite and weight gain in adults. J. Amer. med. Ass.209, 2054–2055 (1969)
Baxter, M.G., Miller, A.A., Soroko, F.E.: The effect of cyproheptadine on food consumption in the fasted rat. Br. J. Pharmacol.39, 229–230 (1970)
Drash, A., Elliot, J., Langs, H., Lavenstein, A.F., Cook, R.E.: The effects of cyproheptadine on carbohydrate metabolism. Clin. Pharmacol. Ther.7, 340–346 (1966)
Wold, J.S., Longnecker, D.S., Fischer, L.J.: Species dependent pancreatic islet toxicity produced by cyproheptadine. Toxicol. appl. Pharmacol.19, 188–201 (1971)
Longnecker, D.S., Wold, J.S., Fischer, L.J.: Ultrastructural alterations in B-cells of pancreatic islets from cyproheptadine treated rats. Diabetes21, 71–79 (1972)
Wellmann, K.F., Volk, B.W., Lazarus, S.S.: Ultrastructural pancreatic B-cell changes in rabbits after small and large doses of alloxan. Diabetes16, 242–251 (1967)
Junod, A., Lambert, A.E., Orci, L., Pictet, R., Gonet, A.E., Renold, A.E.: Studies of the diabetogenic action of streptozotocin. Proc. Soc. exp. Biol. Med.126, 201–205 (1967)
Zarrow, M.X., Yochim, J.M., McCarthy, J.L.: Experimental Endocrinology, p. 308. New York: Academic Press Inc. 1964
Hoffman, W.S.: Rapid photoelectric method for the determination of glucose in blood and urine. J. Biol. Chem.120, 51 (1937)
Lacy, P.E.: Electron microscopic identification of different cell types in the islets of Langerhans of the guinea pig, rat, rabbit and dog. Anat. Rec.128, 255–267 (1957)
Costoff, A.: Ultrastructure of rat adenohypophysis: Correlation with function. Pp. 18, 37, 44 and 74. N. Y. and Ldn. Academic Press 1973
Malaisse, W.J., Malaisse-Lagae, F., King, S., Wright, P.H.: Effect of growth hormone on insulin secretion. Amer. J. Physiol.215, 423–428 (1968)
Bouman, P.R., Bosboom, R.S.: Effects of growth hormone and of hypophysectomy on the release of insulin from rat pancreasin vitro. Acta endocrinol. (Kbh.)50, 202–212 (1965)
Taylor, K.W. Regulation of insulin synthesis. Excerpta Med. Intern. Congr. Ser.184, 220–224 (1968)
Levine, R., Luft, R.: The relation between the growth and diabetogenic effects of the so-called growth hormone of the anterior pituitary. Diabetes13, 651–655 (1964)
Volk, B.W., Lazarus, S.S.: Ultrastructure of pancreatic B-cells in severely diabetic dogs. Diabetes13, 60–70 (1964)
Martin, J.M., Mok, C.C., Penfold, J., Howard, N.J., Crowne, D.: Hypothalamic stimulation of insulin release. J. Endocr.58, 681–682 (1973)
Stevenson, J.A.F.: The Hypothalamus, p. 524. Springfield, Illinois: Charles C. Thomas (1969)
Chakrabarty, A.S., Pillai, R.V., Anand, B.K., Singh, B.: Effects of cyproheptadine on the electrical activity of hypothalamic feeding centres. Brain Res.6, 561–569 (1967)
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Richardson, B.P. Failure of cyproheptadine to induce pancreatic B-cell lesion in hypophysectomized rats. Diabetologia 10, 479–483 (1974). https://doi.org/10.1007/BF01221642
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DOI: https://doi.org/10.1007/BF01221642