Summary
The effects of short-term treatment with either placebo or two serotonin antagonists, cyproheptadine and metergoline, on oral glucose tolerance and insulin secretion have been evaluated in normal subjects and in patients with chemical diabetes. Placebo treatment was not associated with any significant change in the parameters examined. Glucose tolerance in chemical diabetics was significantly improved both after cyproheptadine and metergoline; fasting plasma glucose was also reduced by metergoline. Treatment with the latter drug was also associated with a significant decrease in incremental glucose area in healthy subjects, which was not affected by cyproheptadine. Basal and glucose-stimulated insulin secretion were not affected by either drug in any subjects. Cyproheptadine and metergoline improve glucose metabolism in chemical diabetes probably by reducing insulin resistance. This may depend either on decreased secretion of counter-regulatory hormones or on a direct pharmacological action of the drugs on glucose utilization, possibly mediated by their common antiserotoninergic properties.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Smith, P.H., Porte, D., Jr.: Neuropharmacology of the pancreatic islets. Anne Rev. Pharmacol.16, 269–285 (1976)
Lernmark, A.: The significance of 5-hydroxytryptamine for insulin secretion in the mouse. Horm. Metab. Res.3, 305–309 (1971)
Lebovitz, H.E., Feldman, J.M.: Pancreatic biogenic amines and insulin secretion in health and disease. Fed. Proc.32, 1797–1802 (1973)
Marco, J., Hedo, J. A., Villanueva, M. L.: Inhibition of glucagon release by serotonin in mouse pancreatic islets. Diabetologia13, 585–588 (1977)
Pontiroli, A. E., Micossi, P., Foà, P. P.: Effects of serotonin, of its biosynthetic precursors and of the antiserotonin agent metergoline on the release of glucagon and insulin from rat pancreas. Horm. Metab. Res.10, 200–203 (1978)
Wilson, J. P., Downs, R. W., Feldman, J. M., Lebovitz, H. E.: Beta cell monoamines: further evidence for their role in modulating insulin secretion. Am. J. Physiol.227, 305–312 (1974)
Quickel, K. E., Feldman, J. H., Lebovitz, H. E.: Enhancement of insulin secretion in adult onset diabetics by methysergide maleate: evidence for an endogenous biogenic monoamine mechanism as a factor in the impaired insulin secretion in diabetes mellitus. J. clin. Endocrinol. Metab.33, 877–881 (1971)
Feldman, J. M., Lebovitz, H. E.: Role of pancreatic monoamines in impaired insulin secretion of the fasting state. Endocrinology92, 1469–1475 (1973)
Feldman, J. M., Quickel, K. E., Lebovitz, H. E.: Potentiation of insulin secretion in vitro by serotonin antagonists. Diabetes21, 779–788 (1972)
Marco, J., Hedo, J. A., Martinell, J., Calle, C., Villanueva, M. L.: Potentiation of glucagon secretion by serotonin antagonists in man. J. clin. Endocrinol. Metab.42, 215–221 (1976)
Joost, H. G., Beckmann, J., Holze, S., Lenzen, S., Poser, W., Hasselblatt, A.: Inhibition of insulin and glucagon release from the perfused rat pancreas by cyproheptadine. Diabetologia12, 201–206 (1976)
Mertz, D. P., Stelzer, M.: Zum Mechanismus der appetit- und gewichtsteigernden Wirkung von Cyproheptadin. Veränderungen im Kohlenhydratstoffwechsel. Klin. Wochenschr.47, 1194–1197 (1969)
Fuxe, K., Agnati, L., Everitt, B.: Effects of methergoline on central monoamine neurons. Evidence for a selective blockade of central 5-HT receptors. Neurosci. Lett.1, 283–290 (1975)
Pontiroli, A. E., Viberti, G. C., Tognetti, A., Pozza, G.: Effects of metergoline, a powerful and long-acting antiserotoninergic agent, on insulin secretion in normal subjects and in patients with chemical diabetes. Diabetologia11, 165–167 (1975)
Fajans, S. S., Conn, J. W.: The early recognition of diabetes mellitus. Ann. N. Y. Acad. Sci.82, 208–218 (1959)
Huggett, A. S. G., Nixon, D. A.: Use of glucose oxidase, peroxidase and o-dianisidine in determination of blood and urine glucose. Lancet1957/II, 368–370
Hales, C. N., Randle, P. J.: Immunoassay of insulin with insulin antibody precipitate. Biochem. J.88, 137–146 (1963)
Drash, A., Elliott, J., Langs, H., Lavenstein, A. F., Cooke, R. E.: The effect of cyproheptadine on carbohydrate metabolism. Clin. Pharmacol. Ther.7, 340–346 (1966)
Stone, C. A., Wenger, H. C., Ludden, C. T., Stavorky, J. M., Ross, C. A.: Antiserotonin-antihistaminic properties of cyproheptadine. J. Pharmacol. exp. Ther.131, 73–84 (1961)
Creese, I., Burt, D. R., Snyder, S. H.: The dopamine receptor: differential binding of D-LSD and related agents to antagonist and agonist states. Life Sci.17, 1715–1720 (1975)
Sastry, B. S. R., Phillis, J. W.: Metergoline as a selective 5-hydroxytryptamine antagonist in the cerebral cortex. Can. J. Physiol. Pharmacol.55, 130–133 (1977)
Enjalbert, A., Hamon, M., Bourgoin, S., Bockaert, J.: Postsynaptic serotonin-sensitive adenylate cyclase in the central nervous system. II. Comparison woth dopamine- and isoproterenol-sensitive adenylate cyclase in rat brain. Mol. Pharmacol.14, 11–23 (1978)
Felig, P., Wahren, J., Hendler, R.: Influence of maturity-onset diabetes on splanchnic glucose balance after oral glucose ingestion. Diabetes27, 121–126 (1978)
Beretta, C., Ferrini, R., Glässer, A. H.: 1,6-dimethyl-8-betacarbobenzyloxy-aminomethyl-10 alpha-ergoline, a potent and long-lasting 5-hydroxytryptamine antagonist. Nature207, 421–422 (1965)
Bivens, C. H., Lebovitz, H. E., Feldman, J. M.: Inhibition of hypoglycemia-induced growth hormone secretion by the serotonin antagonists cyproheptadine and methysergide. New Engl. J. Med.289, 236–239 (1973)
Nakai, Y., Imura, H., Sakurai, H., Kurahachi, H., Yoshimi, T.: Effect of cyproheptadine on human growth hormone secretion. J. clin. Endocrinol. Metab.38, 446–449 (1974)
Smythe, G. A., Lazarus, L.: Suppression of human growth hormone secretion by melationin and cyproheptadine. J. clin. Invest.54, 116–121 (1974)
Chihara, H., Kato, Y., Maeda, K., Hatsukura, S., Imura, H.: Suppression by cyproheptadine of human growth hormone and cortisol secretion during sleep. J. clin. Invest.57, 1393–1402 (1976)
Pontiroli, A. E., Viberti, G., Pozza, G.: Growth hormone response to arginine in normal subjects, in patients with chemical diabetes and effect of clofibrate and of metergoline. Proc. Soc. exp. Biol. Med.155, 160–163 (1977)
Plonk, J. W., Bivens, C. H., Feldman, J. M.: Inhibition of hypoglycemia-induced cortisol secretion by the serotonin antagonist cyproheptadine. J. clin. Endocrinol. Metab.38, 836–840 (1974)
Cavagnini, F., Panerai, A. E., Valentini, F., Bulgheroni, P., Peracchi, M., Pinto, M.: Inhibition of ACTH response to oral and I. V. metyrapone by antiserotoninergic treatment in man. J. clin. Endocrinol. Metab.41, 143–148 (1975)
Cavagnini, F., Raggi, U., Micossi, P., Di Sandro, A., Invitti, C.: Effect of an antiserotoninergic drug, metergoline, on the ACTH and cortisol response to insulin hypoglycemia and lysinevasopressin in man. J. clin. Endocrinol. Metab.43, 306–312 (1976)
Ferrari, C., Paracchi, A., Rondena, M., Beck-Peccoz, P., Faglia, G.: Effect of two serotonin antagonists on prolactin and thyrotrophin secretion in man. Clin. Endocrinol.5, 575–578 (1976)
Ferrari, C., Caldara, R., Romussi, M, Rampini, P., Telloli, P., Zaatar, S., Curtarelli, G.: Prolactin suppression by serotonin antagonists in man: further evidence for serotoninergic control of prolactin secretion. Neuroendocrinology25, 319–328 (1978)
Erle, G., Basso, M., Federspil, G., Sicolo, N., Scandellari, C.: Effect of chlorpromazine on blood glucose and plasma insulin in man. Europ. J. clin. Pharmacol.11, 15–18 (1977)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ferrari, C., Barbieri, C., Caldara, R. et al. Improved oral glucose tolerance following antiserotonin treatment in patients with chemical diabetes. Eur J Clin Pharmacol 15, 395–399 (1979). https://doi.org/10.1007/BF00561737
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00561737