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. 1996 Jan;117(2):347–350. doi: 10.1111/j.1476-5381.1996.tb15197.x

Effect of (8-32) salmon calcitonin, an amylin antagonist, on insulin, glucagon and somatostatin release: study in the perfused pancreas of the rat.

R A Silvestre 1, M Salas 1, J Rodríguez-Gallardo 1, O García-Hermida 1, T Fontela 1, J Marco 1
PMCID: PMC1909271  PMID: 8789389

Abstract

1. The 8-32 fragment of salmon calcitonin ((8-32) sCT) has been proposed as a highly selective amylin receptor antagonist. 2. In the present study, we have studied the influence of (8-32) sCT on the inhibitory effect of both amylin and its structural congener, calcitonin gene-related peptide (CGRP), on insulin secretion in the rat perfused pancreas. 3. Both amylin and CGRP, at 75 pM, clearly inhibited glucose-induced insulin release (by 80% and by 70%, respectively). Simultaneous infusion of 10 microM (8-32) sCT reversed the inhibitory effect of amylin (by 80%; P < 0.05 vs. amylin experiments) but did not significantly affect the inhibition of glucose-induced insulin output elicited by CGRP. Furthermore, at the same concentration (10 microM), (8-32) sCT alone potentiated the insulin response to 7 mM glucose (2.5 fold; P < 0.05) whilst it did not affect glucagon or somatostatin secretion. 4. The observation that infusion of an amylin antagonist into the rat pancreas potentiates the insulin response to glucose, favours the concept of endogenous amylin as an inhibitor of insulin release. 5. Finally, as an amylin antagonist at the level of the beta-cell, (8-32) sCT might be considered of potential interest in experimental and clinical pharmacology.

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Selected References

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  1. Alwmark A., Stavinoha M. W., Cooper C. W., Greeley G. H., Jr, Thompson J. C. Calcitonin inhibition of insulin release from isolated rat pancreatic islets. Diabetes. 1986 Jan;35(1):58–60. doi: 10.2337/diab.35.1.58. [DOI] [PubMed] [Google Scholar]
  2. Barakat A., Rosselin G., Marie J. C. Characterization of specific calcitonin gene-related peptide receptors present in hamster pancreatic beta cells. Biosci Rep. 1993 Aug;13(4):221–231. doi: 10.1007/BF01123504. [DOI] [PubMed] [Google Scholar]
  3. Bhogal R., Smith D. M., Bloom S. R. Investigation and characterization of binding sites for islet amyloid polypeptide in rat membranes. Endocrinology. 1992 Feb;130(2):906–913. doi: 10.1210/endo.130.2.1310282. [DOI] [PubMed] [Google Scholar]
  4. D'Alessio D. A., Verchere C. B., Kahn S. E., Hoagland V., Baskin D. G., Palmiter R. D., Ensinck J. W. Pancreatic expression and secretion of human islet amyloid polypeptide in a transgenic mouse. Diabetes. 1994 Dec;43(12):1457–1461. doi: 10.2337/diab.43.12.1457. [DOI] [PubMed] [Google Scholar]
  5. Dégano P., Silvestre R. A., Salas M., Peiró E., Marco J. Amylin inhibits glucose-induced insulin secretion in a dose-dependent manner. Study in the perfused rat pancreas. Regul Pept. 1993 Jan 22;43(1-2):91–96. doi: 10.1016/0167-0115(93)90411-z. [DOI] [PubMed] [Google Scholar]
  6. Fehmann H. C., Weber V., Göke R., Göke B., Eissele R., Arnold R. Islet amyloid polypeptide (IAPP;amylin) influences the endocrine but not the exocrine rat pancreas. Biochem Biophys Res Commun. 1990 Mar 30;167(3):1102–1108. doi: 10.1016/0006-291x(90)90636-2. [DOI] [PubMed] [Google Scholar]
  7. Harris V., Conlon J. M., Srikant C. B., McCorkle K., Schusdziarra V., Ipp E., Unger R. H. Measurements of somatostatin-like immunoreactivity in plasma. Clin Chim Acta. 1978 Jul 15;87(2):275–283. doi: 10.1016/0009-8981(78)90348-0. [DOI] [PubMed] [Google Scholar]
  8. Herbert V., Lau K. S., Gottlieb C. W., Bleicher S. J. Coated charcoal immunoassay of insulin. J Clin Endocrinol Metab. 1965 Oct;25(10):1375–1384. doi: 10.1210/jcem-25-10-1375. [DOI] [PubMed] [Google Scholar]
  9. Höppener J. W., Verbeek J. S., de Koning E. J., Oosterwijk C., van Hulst K. L., Visser-Vernooy H. J., Hofhuis F. M., van Gaalen S., Berends M. J., Hackeng W. H. Chronic overproduction of islet amyloid polypeptide/amylin in transgenic mice: lysosomal localization of human islet amyloid polypeptide and lack of marked hyperglycaemia or hyperinsulinaemia. Diabetologia. 1993 Dec;36(12):1258–1265. doi: 10.1007/BF00400803. [DOI] [PubMed] [Google Scholar]
  10. Kogire M., Ishizuka J., Thompson J. C., Greeley G. H., Jr Inhibitory action of islet amyloid polypeptide and calcitonin gene-related peptide on release of insulin from the isolated perfused rat pancreas. Pancreas. 1991 Jul;6(4):459–463. doi: 10.1097/00006676-199107000-00013. [DOI] [PubMed] [Google Scholar]
  11. Lukinius A., Wilander E., Westermark G. T., Engström U., Westermark P. Co-localization of islet amyloid polypeptide and insulin in the B cell secretory granules of the human pancreatic islets. Diabetologia. 1989 Apr;32(4):240–244. doi: 10.1007/BF00285291. [DOI] [PubMed] [Google Scholar]
  12. Lunetta M., Infantone E., Spanti D., Mughini L. Effects of synthetic salmon calcitonin administration on gastrin, immunoreactive insulin and growth hormone release after protein meal in uremic patients. J Endocrinol Invest. 1981 Apr-Jun;4(2):185–188. doi: 10.1007/BF03350449. [DOI] [PubMed] [Google Scholar]
  13. Nagamatsu S., Carroll R. J., Grodsky G. M., Steiner D. F. Lack of islet amyloid polypeptide regulation of insulin biosynthesis or secretion in normal rat islets. Diabetes. 1990 Jul;39(7):871–874. doi: 10.2337/diab.39.7.871. [DOI] [PubMed] [Google Scholar]
  14. O'Brien T. D., Westermark P., Johnson K. H. Islet amyloid polypeptide (IAPP) does not inhibit glucose-stimulated insulin secretion from isolated perfused rat pancreas. Biochem Biophys Res Commun. 1990 Aug 16;170(3):1223–1228. doi: 10.1016/0006-291x(90)90524-q. [DOI] [PubMed] [Google Scholar]
  15. Peiró E., Dégano P., Silvestre R. A., Marco J. Inhibition of insulin release by amylin is not mediated by changes in somatostatin output. Life Sci. 1991;49(10):761–765. doi: 10.1016/0024-3205(91)90109-o. [DOI] [PubMed] [Google Scholar]
  16. Pettersson M., Ahrén B. Failure of islet amyloid polypeptide to inhibit basal and glucose-stimulated insulin secretion in model experiments in mice and rats. Acta Physiol Scand. 1990 Mar;138(3):389–394. doi: 10.1111/j.1748-1716.1990.tb08861.x. [DOI] [PubMed] [Google Scholar]
  17. Porte D., Jr, Kahn S. E. Hyperproinsulinemia and amyloid in NIDDM. Clues to etiology of islet beta-cell dysfunction? Diabetes. 1989 Nov;38(11):1333–1336. doi: 10.2337/diab.38.11.1333. [DOI] [PubMed] [Google Scholar]
  18. Silvestre R. A., Miralles P., Moreno P., Villanueva M. L., Marco J. Somatostatin, insulin and glucagon secretion by the perfused pancreas from the cysteamine-treated rat. Biochem Biophys Res Commun. 1986 Feb 13;134(3):1291–1297. doi: 10.1016/0006-291x(86)90390-6. [DOI] [PubMed] [Google Scholar]
  19. Silvestre R. A., Peiró E., Dégano P., Miralles P., Marco J. Inhibitory effect of rat amylin on the insulin responses to glucose and arginine in the perfused rat pancreas. Regul Pept. 1990 Oct 29;31(1):23–31. doi: 10.1016/0167-0115(90)90192-y. [DOI] [PubMed] [Google Scholar]
  20. Silvestre R. A., Salas M., Dégano P., Peiró E., Marco J. Reversal of the inhibitory effects of calcitonin gene-related peptide (CGRP) and amylin on insulin secretion by the 8-37 fragment of human CGRP. Biochem Pharmacol. 1993 Jun 9;45(11):2343–2347. doi: 10.1016/0006-2952(93)90209-f. [DOI] [PubMed] [Google Scholar]
  21. Silvestre R. A., Salas M., García-Hermida O., Fontela T., Dégano P., Marco J. Amylin (islet amyloid polypeptide) inhibition of insulin release in the perfused rat pancreas: implication of the adenylate cyclase/cAMP system. Regul Pept. 1994 Feb 24;50(2):193–199. doi: 10.1016/0167-0115(94)90035-3. [DOI] [PubMed] [Google Scholar]
  22. Tedstone A. E., Nezzer T., Hughes S. J., Clark A., Matthews D. R. The effect of islet amyloid polypeptide (amylin) and calcitonin gene-related peptide on glucose removal in the anaesthetized rat and on insulin secretion from rat pancreatic islets in vitro. Biosci Rep. 1990 Aug;10(4):339–345. doi: 10.1007/BF01117233. [DOI] [PubMed] [Google Scholar]
  23. Verchere C. B., D'Alessio D. A., Palmiter R. D., Kahn S. E. Transgenic mice overproducing islet amyloid polypeptide have increased insulin storage and secretion in vitro. Diabetologia. 1994 Jul;37(7):725–728. doi: 10.1007/BF00417699. [DOI] [PubMed] [Google Scholar]
  24. Wagoner P. K., Chen C., Worley J. F., Dukes I. D., Oxford G. S. Amylin modulates beta-cell glucose sensing via effects on stimulus-secretion coupling. Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9145–9149. doi: 10.1073/pnas.90.19.9145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Wang Z. L., Bennet W. M., Ghatei M. A., Byfield P. G., Smith D. M., Bloom S. R. Influence of islet amyloid polypeptide and the 8-37 fragment of islet amyloid polypeptide on insulin release from perifused rat islets. Diabetes. 1993 Feb;42(2):330–335. doi: 10.2337/diab.42.2.330. [DOI] [PubMed] [Google Scholar]
  26. YALOW R. S., BERSON S. A. Immunoassay of endogenous plasma insulin in man. J Clin Invest. 1960 Jul;39:1157–1175. doi: 10.1172/JCI104130. [DOI] [PMC free article] [PubMed] [Google Scholar]

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