Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1980 Nov;70(3):355–362. doi: 10.1111/j.1476-5381.1980.tb08710.x

Mechanism by which cyproheptadine inhibits insulin secretion.

P Donatsch, D A Lowe, B P Richardson, P Taylor
PMCID: PMC2044340  PMID: 7002245

Abstract

1 Isolated islets of Langerhans from the rat have been used in studies designed to elucidate the mechanism by which cyproheptadine inhibits insulin secretion. 2 D-Glucose and tolbutamide, both of which require extracellular Ca2+ to produce insulin release, failed to evoke a secretory response from islets pretreated with cyproheptadine. Conversely veratridine, the calcium ionophore A23187 and theophylline, all of which are capable of mobilizing sufficient intracellular Ca2+ to evoke insulin secretion in the absence of extracellular Ca2+, produced similar responses from cyproheptadine pretreated and control islets. 3 Cyproheptadine completely inhibited Ca2+ uptake induced by D-glucose and high Ko+, two agents which depolarize the islet beta-cell membrane, whilst Ca2+ uptake elicited by removal of extracellular Na+ (i.e. Na+-Ca2+ counter transport) was only slightly reduced. 4 A significant increase in Na+ uptake produced by veratridine was sensitive to tetrodoxin but only partially reduced by cyproheptadine. 5 These results suggest that cyproheptadine inhibits depolarization-dependent calcium entry into pancreatic beta-cells.

Full text

PDF
355

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ashby J. P., Speake R. N. Insulin and glucagon secretion from isolated islets of Langerhans. The effects of calcium ionophores. Biochem J. 1975 Jul;150(1):89–96. [PMC free article] [PubMed] [Google Scholar]
  2. Baker P. F. Regulation of intracellular Ca and Mg in squid axons. Fed Proc. 1976 Dec;35(14):2589–2595. [PubMed] [Google Scholar]
  3. Brisson G. R., Malaisse-Lagae F., Malaisse W. J. The stimulus-secretion coupling of glucose-induced insulin release. VII. A proposed site of action for adenosine-3',5'-cyclic monophosphate. J Clin Invest. 1972 Feb;51(2):232–241. doi: 10.1172/JCI106808. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Charles M. A., Lawecki J., Pictet R., Grodsky G. M. Insulin secretion. Interrelationships of glucose, cyclic adenosine 3:5-monophosphate, and calcium. J Biol Chem. 1975 Aug 10;250(15):6134–6140. [PubMed] [Google Scholar]
  5. Dean P. M., Matthews E. K. Electrical activity in pancreatic islet cells: effect of ions. J Physiol. 1970 Sep;210(2):265–275. doi: 10.1113/jphysiol.1970.sp009208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dean P. M., Matthews E. K., Sakamoto Y. Pancreatic islet cells: effects of monosaccharides, glycolytic intermediates and metabolic inhibitors on membrane potential and electrical activity. J Physiol. 1975 Mar;246(2):459–478. doi: 10.1113/jphysiol.1975.sp010899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Feldman J. M., Chapman B. A., Plonk J. W. Monoamine oxidase inhibition: possible mechanism for cyproheptadine-induced alterations in insulin secretion. Life Sci. 1974 Sep 15;15(6):1121–1134. doi: 10.1016/s0024-3205(74)80009-3. [DOI] [PubMed] [Google Scholar]
  8. 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 (Periactinol, Nuran). Diabetologia. 1976 Jul;12(3):201–206. doi: 10.1007/BF00422086. [DOI] [PubMed] [Google Scholar]
  9. Joost H. G., Poser W., Panten U. Inhibition of insulin release from the rat pancreas by cyproheptadine and tricyclic antidepressants. Naunyn Schmiedebergs Arch Pharmacol. 1974;285(1):99–102. doi: 10.1007/BF00499530. [DOI] [PubMed] [Google Scholar]
  10. Karl R. C., Zawalich W. S., Ferrendelli J. A., Matschinsky F. M. The role of Ca-2+ and cyclic adenosine 3':5'-monophosphate in insulin release induced in vitro by the divalent cation ionophore A23187. J Biol Chem. 1975 Jun 25;250(12):4575–4579. [PubMed] [Google Scholar]
  11. Lacy P. E., Kostianovsky M. Method for the isolation of intact islets of Langerhans from the rat pancreas. Diabetes. 1967 Jan;16(1):35–39. doi: 10.2337/diab.16.1.35. [DOI] [PubMed] [Google Scholar]
  12. Lacy P. E., Walker M. M., Fink C. J. Perifusion of isolated rat islets in vitro. Participation of the microtubular system in the biphasic release of insulin. Diabetes. 1972 Oct;21(10):987–998. doi: 10.2337/diab.21.10.987. [DOI] [PubMed] [Google Scholar]
  13. Lowe D. A., Richardson N. P., Taylor P., Donatsch P. Increasing intracellular sodium triggers calcium release from bound pools. Nature. 1976 Mar 25;260(5549):337–338. doi: 10.1038/260337a0. [DOI] [PubMed] [Google Scholar]
  14. Malaisse-Lagae F., Malaisse W. J. The stimulus-secretion coupling of glucose-induced insulin release. 3. Uptake of 45 calcium by isolated islets of Langerhans. Endocrinology. 1971 Jan;88(1):72–80. doi: 10.1210/endo-88-1-72. [DOI] [PubMed] [Google Scholar]
  15. Malaisse W. J. Insulin secretion: multifactorial regulation for a single process of release. The Minkowski award lecture delivered on September 7, 1972 before the European Association for the study of Diabetes at Madrid, Spain. Diabetologia. 1973 Jun;9(3):167–173. doi: 10.1007/BF01219778. [DOI] [PubMed] [Google Scholar]
  16. Matthews E. K., Sakamoto Y. Electrical characteristics of pancreatic islet cells. J Physiol. 1975 Mar;246(2):421–437. doi: 10.1113/jphysiol.1975.sp010897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Richardson B. P., Berde B. Proceedings: The effects of cyproheptadine pretreatment on insulin release from isolated pancreatic islets. Br J Pharmacol. 1976 Mar;56(3):356P–357P. [PMC free article] [PubMed] [Google Scholar]
  18. Richardson B. P., McDaniel M. L., Lacy P. E. Effects of cyproheptadine on insulin secretion by isolated perifused rat islets. Diabetes. 1975 Sep;24(9):836–841. doi: 10.2337/diab.24.9.836. [DOI] [PubMed] [Google Scholar]
  19. Rickert D. E., Fischer L. J. Cyproheptadine and beta cell function in the rat: insulin secretion from pancreas segments in vitro. Proc Soc Exp Biol Med. 1975 Oct;150(1):1–6. doi: 10.3181/00379727-150-38961. [DOI] [PubMed] [Google Scholar]
  20. Seeman P. The membrane actions of anesthetics and tranquilizers. Pharmacol Rev. 1972 Dec;24(4):583–655. [PubMed] [Google Scholar]
  21. Wright P. H., Makulu D. R., Vichick D., Sussman K. E. Insulin immunoassay by back-titration; some characteristics of the technic and the insulin precipitant action of alcohol. Diabetes. 1971 Jan;20(1):33–45. doi: 10.2337/diab.20.1.33. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES