Journal of Endocrinological Investigation

, Volume 9, Issue 3, pp 209–215 | Cite as

Effects of beta non-selective and beta1 selective adrenergic blocking agents on glucagon secretion from isolated perfused rat pancreas

  • F. Gregorio
  • P. Filipponi
  • S. Cristallini
  • C. Carloni
  • I. Moretti
  • C. Ferrandina
  • R. Pippi
  • M. Pietropaolo


To characterize beta-receptors which affect pancreatic A-cell activity, the effects of propranolol (beta non-selective blockade) and metoprolol (beta1 selective blockade) were evaluated on epinephrine modulated insulin (IRI) and glucagon (IRG) release both in basal state and during metabolic stimulus (arginine 20 mM). The isolated perfused rat pancreas model with the exclusion of stomach and duodenum was used. Epinephrine infusion (at 10−7 M) caused a prompt and sustained increase in basal IRG secretion and significantly potentiated glucagon release in response to metabolic stimulus. Insulin secretion was markedly suppressed by epinephrine both in basal conditions and during metabolic stimulus. Propranolol (at 10−7 M) and metoprolol (at 10−7 M) infusion clearly and similarly counteracted epinephrine stimulatory effects on IRG secretion but failed to elicit any significant effect on the epinephrine inhibited IRI release either in basal state or during the metabolic stimulus. These results suggest that, at least in the rat, the adrenergic stimulation of IRG release is mediated through a beta1 receptor.


Beta (non) selective blockade adrenergic control glucagon secretion isolated perfused pancreas 


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  1. 1.
    Ahlquist R.P. A study of adrenotropic receptors. Am. J. Physiol. 153: 587, 1984.Google Scholar
  2. 2.
    Lands A.M., Arnold A., McAuliff J.P., Luduena F.P., Brown R.G. Differentiation of receptor systems activated by sympathomimetic amines. Nature 214: 597, 1967PubMedCrossRefGoogle Scholar
  3. 3.
    Iversen J. Adrenergic receptors and the secretion of glucagon and insulin from the isolated perfused canine pancreas. J. Clin. Invest. 52: 2102, 1973.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Gerich J., Langlois M., Noacco C., Schneider V., Forsham P. Adrenergic modulation of pancreatic glucagon secretion in man. J. Clin. Invest. 53: 1441, 1974.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Samols E., Weir G.C. Adrenergic modulation of pancreatic A, B and D cells. J. Clin. Invest. 63: 230, 1979.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Patel D.G. Role of sympathetic nervous system in glucagon response to insulin hypoglycemia in normaf and diabetic rats. Diabetes 33: 1154, 1984.PubMedCrossRefGoogle Scholar
  7. 7.
    Loubatières-Mariani M.M., Chapal J., Ribes G., Loubatières A.L. Discrepancies in the response of the insulin secreting cells of the dog and rat to different adrenergic stimulating agents. Acta. Diabetol. Lat. 14: 144, 1977.PubMedCrossRefGoogle Scholar
  8. 8.
    Nakaki T., Nakadate T., Kato R. Alpha2-adrenoreceptors modulating insulin release from isolated pancreatic islets. Naunyn Schmiedeberg’s Arch. Pharmacol. 313: 151, 1980.CrossRefGoogle Scholar
  9. 9.
    Nakadate T., Nakaki T., Muraki T., Kato R. Adrenergic regulation of blood glucose levels: possible involvement of postsynaptic alpha2-type adrenergic receptors regulating insulin release. J. Pharmacol. Exp.Ther. 215: 226, 1980.PubMedGoogle Scholar
  10. 10.
    Hsu M.W., Hummel Sharon K. Xylazine-Induced hyperglycemia in cattle: a possible involvement of alpha2 adrenergic receptors regulating insulin release. Endocrinology 109: 825, 1981.PubMedCrossRefGoogle Scholar
  11. 11.
    Cherksey N., Mendelsohn S., Zadunaisky J., Altszuler N. Demonstration of alpha2 adrenergic receptors in rat pancreatic islets using radioligand bindings. Proc. Soc. Exp. Biol. Med. 171: 196, 1982.PubMedCrossRefGoogle Scholar
  12. 12.
    Filipponi P., Marcelli M., Nicoletti I., Santeusanio F., Pacifici R., Brunetti P. Characterization of adrenergic control of glucagon secretion from isolated perfused rat pancreas. Diabete Metab. 8: 313, 1982.PubMedGoogle Scholar
  13. 13.
    Kato R., Nakaki T. Alpha2 adrenoreceptor beyong cAMP generation: islet of Langerhans and intestinal epithelium. THPS: 34, 1983.Google Scholar
  14. 14.
    Kaneto A., Miki E., Kosaka K. Effect of beta2 adrenoreceptor stimulants infused intrapancreatically on glucagon and insulin secretion. Endocrinology 97: 1166, 1975.PubMedCrossRefGoogle Scholar
  15. 15.
    Day J.L., Simpson N., Metcalfe J., Page R.L. Metabolic consequences of atenolol in treatment of essential hypertension. Br. Med. J. 1: 77, 1979.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Gundogdu A.S., Brown P.M., Juul S., Sachs L., Sonksen P.H. Comparison of hormonal and metabolic effects of salbutamol infusion in normal subjects and insulin-requiring diabetics. Lancet II: 1317, 1979.CrossRefGoogle Scholar
  17. 17.
    De Feo P., Bolli G., Perriello G., De Cosmo S., Compagnucci P., Angeletti G., Santeusanio F., Gerich J.E., Motolese M., Brunetti P. The adrenergic contribution to glucose counterregulation in type 1 diabetes mellitus. Dependency on A-cell function and mediation through beta2-adrenergic receptors. Diabetes 32: 887, 1983.PubMedCrossRefGoogle Scholar
  18. 18.
    Lauridsen U.B., Christensen N.J., Lyngsoe J. Effects of nonselective and B1-selective blockade on glucose metabolism and hormone responses during insulin-induced hypoglycemia in normal man. J. Clin. Endocrinol. Metab. 56: 876, 1983.PubMedCrossRefGoogle Scholar
  19. 19.
    Corrall R.J.M., Frier B.M., Davidson N. McD., French E.B. Hormonal and substrate responses during recovery from hypoglycemia in man during beta1 -selective and non-selective beta-adrenergic blockade. Eur. J. Clin. Invest. 11: 279, 1981.PubMedCrossRefGoogle Scholar
  20. 20.
    Sussman K.R., Vaughan G.D., Timmer R.F. An in vitro method for studying insulin secretion in the perfused isolated rat pancreas. Metabolism 75: 466, 1966.CrossRefGoogle Scholar
  21. 21.
    Filipponi P., Gregorio F., Marcelli M., Nicoletti I., Ferrandina C., Gubbiotti G., Pippi R., Santeusanio F. In vitro effect of A1 and A2 adrenergic blockers of epinephrine-induced inhibition of pancreatic B-cell function. Diabetes 33(Suppl. 1): 590, 1984.Google Scholar
  22. 22.
    Herbert V., Lav K.S., Gottlieb G.W., Bleischer S.J. Coated charcoal immunoassay of insulin. J. Clin. Endocrinol. Metab. 25: 1375, 1965.PubMedCrossRefGoogle Scholar
  23. 23.
    Heding LG. Radioimmunoassay determination of pancreatic and gut glucagon in plasma. Diabetologia 7: 10, 1971.PubMedCrossRefGoogle Scholar
  24. 24.
    Gerich J.E., Lorenzi M. The role of autonomic nervous system and somatostatin in the control of insulin and glucagon secretion. In: Ganong W.F., Martini L. (Eds.), Frontiers in Neuroendocrinology. Raven Press, New York, 1978, p. 265.Google Scholar
  25. 25.
    Luyckx A.S., Lefebvre P.J. Mechanism involved in the exercise-induced increase in glucagon secretion in rats. Diabetes 23: 81, 1974.PubMedGoogle Scholar
  26. 26.
    Lager I., Jagenburg R., v. Schenck H., Smith U. Effect of beta-blockade on hormone release during hypoglycemia in insulin-dependent diabetics. Acta Endocrihol. (Kbh.) 95: 364, 1980.Google Scholar
  27. 27.
    Areins E.J., Simonis A.M. Physiological and pharmacological aspects of adrenergic receptor classification. Biochem. Pharmacol. 32: 1539, 1983.CrossRefGoogle Scholar
  28. 28.
    Taylor M.W., Gaddie J., Murchison LE., Palmer K.N.V. Metabolic effects of oral salbutamol. Br. Med.J. I: 22, 1976.CrossRefGoogle Scholar
  29. 29.
    Thomas D.J.B., Dove A.F., Alberti K.G.M.M. Metabolic effects of salbutamol infusion during premature labour. Br. J. Obstet. Gynaecol. 84: 497, 1977.PubMedCrossRefGoogle Scholar
  30. 30.
    William-Olsson T., Fellenius E., Bjorntorp P., Smith U. Differences in metabolic responses to B-adrenergic stimulation after propranolol or metoprolol administration. Acta Med. Scand. 205: 201, 1979.PubMedCrossRefGoogle Scholar
  31. 31.
    Cotton D.B., Strassner H.T., Lipson L.G., Goldstein D.A. The effects of terbutaline on acid base, serum electrolytes, and glucose homeostasis during the management of preterm labor. Am. J. Obstet. Gynecol. 147: 617, 1981.Google Scholar
  32. 32.
    Goldberg R., Joffe B.I., Bersohn I., Van As M., Krut L., Seftel H.C. Metabolic responses to selective B-adrenergic stimulation in man. Postgrad. Med. J. 51: 53, 1975.PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Loubatières A., Mariani M.M., Sorel G., Savi L. The action of β-adrenergic blocking and stimulating agent on insulin secretion. Characterization of the type of β-receptor. Diabetologia 7: 127, 1971.PubMedCrossRefGoogle Scholar
  34. 34.
    Massi Benedetti M., Santeusanio F., Filipponi P., Nicoletti I., Santori P., Angeletti G. Effect of salbutamol infusion on insulin and glucagon secretion in normal man. I.R.C.S. 10: 12, 1982.Google Scholar
  35. 35.
    Scheidegger K., Robbins D.C., Danforth Jr. E. Effects of chronic beta receptor stimulation on glucose metabolism. Diabetes 33: 1144, 1984.PubMedCrossRefGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 1986

Authors and Affiliations

  • F. Gregorio
    • 1
  • P. Filipponi
    • 1
  • S. Cristallini
    • 1
  • C. Carloni
    • 1
  • I. Moretti
    • 1
  • C. Ferrandina
    • 1
  • R. Pippi
    • 2
  • M. Pietropaolo
    • 2
  1. 1.Istituto di Clinica Medica I, Policlinico MontelucePerugiaItaly
  2. 2.Istituto di Patologia Speciale Medica, Policlinico MontelucePerugiaItaly

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