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. 1991 Jul;103(3):1824–1828. doi: 10.1111/j.1476-5381.1991.tb09870.x

Selective stimulation of glucagon secretion by beta 2-adrenoceptors in isolated islets of Langerhans of the rat.

R J Lacey 1, N S Berrow 1, J H Scarpello 1, N G Morgan 1
PMCID: PMC1907811  PMID: 1718526

Abstract

1. In rat isolated islets of Langerhans the selective beta 2-adrenoceptor agonist, clenbuterol (1 to 20 microM), significantly increased the level of adenosine 3':5'-cyclic monophosphate (cyclic AMP) within 2 min of incubation. 2. The cyclic AMP response to clenbuterol was inhibited in the presence of the selective beta 2 adrenoceptor antagonist, ICI 118551 (0.1 or 10 microM) but remained unchanged when the beta 1-antagonist, atenolol (0.1 microM) was administered. 3. Despite causing an elevation in cyclic AMP, clenbuterol (up to 20 microM) failed to influence insulin secretion at any glucose concentration tested, even in the presence of a phosphodiesterase inhibitor. 4. By contrast, clenbuterol elicited a dose-dependent rise in the rate of glucagon secretion; the maximal agonist-induced increase in secretion was two fold, a response equivalent to that observed with 20 mM L-arginine. 5. ICI 118551 significantly inhibited the rise in glucagon secretion induced by clenbuterol (up to 20 microM). 6. The results indicate that the rat islet A cell population is equipped with functional beta 2-adrenoceptors which influence glucagon secretion via the second messenger cyclic AMP, but that the B cells are deficient in functional beta-receptors.

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Selected References

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  1. Ahrén B., Lundquist I. Alpha-adrenoceptor blockade by phentolamine inhibits beta-adrenergically and cholinergically induced glucagon secretion in the mouse. Horm Metab Res. 1987 Dec;19(12):600–603. doi: 10.1055/s-2007-1011889. [DOI] [PubMed] [Google Scholar]
  2. Bjaaland T., Hii C. S., Jones P. M., Howell S. L. Role of protein kinase C in arginine-induced glucagon secretion from isolated rat islets of Langerhans. J Mol Endocrinol. 1988 Sep;1(2):105–110. doi: 10.1677/jme.0.0010105. [DOI] [PubMed] [Google Scholar]
  3. Brown B. L., Albano J. D., Ekins R. P., Sgherzi A. M. A simple and sensitive saturation assay method for the measurement of adenosine 3':5'-cyclic monophosphate. Biochem J. 1971 Feb;121(3):561–562. doi: 10.1042/bj1210561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cherksey B., Altszuler N., Zadunaisky J. Preponderance of beta-adrenergic binding sites in pancreatic islet cells of the rat. Diabetes. 1981 Feb;30(2):172–174. doi: 10.2337/diab.30.2.172. [DOI] [PubMed] [Google Scholar]
  5. Faure A., Haouari M., Sutter B. C. Short term and direct influence of oestradiol on glucagon secretion stimulated by arginine. Diabete Metab. 1988 Jul-Aug;14(4):452–454. [PubMed] [Google Scholar]
  6. Fyles J. M., Cawthorne M. A., Howell S. L. The characteristics of beta-adrenergic binding sites on pancreatic islets of Langerhans. J Endocrinol. 1986 Nov;111(2):263–270. doi: 10.1677/joe.0.1110263. [DOI] [PubMed] [Google Scholar]
  7. Gerich J. E., Langlois M., Noacco C., Schneider V., Forsham P. H. Adrenergic modulation of pancreatic glucagon secretion in man. J Clin Invest. 1974 May;53(5):1441–1446. doi: 10.1172/JCI107692. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hermann L. S., Deckert T. The effect of epinephrine and isoproterenol on insulin secretion and glucose utilization in isolated islets of Langerhans from mice. Acta Endocrinol (Copenh) 1977 Jan;84(1):105–114. doi: 10.1530/acta.0.0840105. [DOI] [PubMed] [Google Scholar]
  9. Howell S. L., Montague W. Adenylate cyclase activity in isolated rat islets of Langerhans. Effects of agents which alter rates of insulin secretion. Biochim Biophys Acta. 1973 Aug 17;320(1):44–52. doi: 10.1016/0304-4165(73)90163-3. [DOI] [PubMed] [Google Scholar]
  10. Itoh M., Gerich J. E. Adrenergic modulation of pancreatic somatostatin, insulin, and glucagon secretion: evidence for differential sensitivity of islet A, B, and D cells. Metabolism. 1982 Jul;31(7):715–720. doi: 10.1016/0026-0495(82)90203-7. [DOI] [PubMed] [Google Scholar]
  11. Iversen J. Adrenergic receptors and the secretion of glucagon and insulin from the isolated, perfused canine pancreas. J Clin Invest. 1973 Sep;52(9):2102–2116. doi: 10.1172/JCI107395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. John G. W., Doxey J. C., Walter D. S., Reid J. L. The role of alpha- and beta-adrenoceptor subtypes in mediating the effects of catecholamines on fasting glucose and insulin concentrations in the rat. Br J Pharmacol. 1990 Aug;100(4):699–704. doi: 10.1111/j.1476-5381.1990.tb14078.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kaneto A., Miki E., Kosaka K. Effects of vagal stimulation on glucagon and insulin secretion. Endocrinology. 1974 Oct;95(4):1005–1010. doi: 10.1210/endo-95-4-1005. [DOI] [PubMed] [Google Scholar]
  14. Lacey R. J., Berrow N. S., London N. J., Lake S. P., James R. F., Scarpello J. H., Morgan N. G. Differential effects of beta-adrenergic agonists on insulin secretion from pancreatic islets isolated from rat and man. J Mol Endocrinol. 1990 Aug;5(1):49–54. doi: 10.1677/jme.0.0050049. [DOI] [PubMed] [Google Scholar]
  15. Lefkowitz R. J., Caron M. G. Adrenergic receptors. Models for the study of receptors coupled to guanine nucleotide regulatory proteins. J Biol Chem. 1988 Apr 15;263(11):4993–4996. [PubMed] [Google Scholar]
  16. Miller R. E. Pancreatic neuroendocrinology: peripheral neural mechanisms in the regulation of the Islets of Langerhans. Endocr Rev. 1981 Fall;2(4):471–494. doi: 10.1210/edrv-2-4-471. [DOI] [PubMed] [Google Scholar]
  17. Montague W., Taylor K. W. Pentitols and insulin release by isolated rat islets of Langerhans. Biochem J. 1968 Sep;109(3):333–339. doi: 10.1042/bj1090333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Morgan N. G., Montague W. Studies on the mechanism of inhibition of glucose-stimulated insulin secretion by noradrenaline in rat islets of Langerhans. Biochem J. 1985 Mar 1;226(2):571–576. doi: 10.1042/bj2260571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Nakaki T., Nakadate T., Yamamoto S., Kato R. Inhibition of dibutyryl cyclic AMP-induced insulin release by alpha-2 adrenergic stimulation. Life Sci. 1983 Jan 17;32(3):191–195. doi: 10.1016/0024-3205(83)90030-9. [DOI] [PubMed] [Google Scholar]
  20. Orci L. The insulin factory: a tour of the plant surroundings and a visit to the assembly line. The Minkowski lecture 1973 revisited. Diabetologia. 1985 Aug;28(8):528–546. doi: 10.1007/BF00281987. [DOI] [PubMed] [Google Scholar]
  21. Porte D., Jr Beta adrenergic stimulation of insulin release in man. Diabetes. 1967 Mar;16(3):150–155. doi: 10.2337/diab.16.3.150. [DOI] [PubMed] [Google Scholar]
  22. Ribes G., Trimble E. R., Blayac J. P., Wollheim C. B., Loubatières-Mariani M. M. In vivo stimulation of pancreatic hormone secretion by norepinephrine infusion in the dog. Am J Physiol. 1984 Apr;246(4 Pt 1):E339–E343. doi: 10.1152/ajpendo.1984.246.4.E339. [DOI] [PubMed] [Google Scholar]
  23. Samols E., Weir G. C. Adrenergic modulation of pancreatic A, B, and D cells alpha-Adrenergic suppression and beta-adrenergic stimulation of somatostatin secretion, alpha-adrenergic stimulation of glucagon secretion in the perfused dog pancreas. J Clin Invest. 1979 Feb;63(2):230–238. doi: 10.1172/JCI109294. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Schuit F. C., Derde M. P., Pipeleers D. G. Sensitivity of rat pancreatic A and B cells to somatostatin. Diabetologia. 1989 Mar;32(3):207–212. doi: 10.1007/BF00265096. [DOI] [PubMed] [Google Scholar]
  25. Schuit F. C., Pipeleers D. G. Differences in adrenergic recognition by pancreatic A and B cells. Science. 1986 May 16;232(4752):875–877. doi: 10.1126/science.2871625. [DOI] [PubMed] [Google Scholar]
  26. Zielmann S., Schütte G., Lenzen S., Panten U. Effects of isoprenaline and glucagon on insulin secretion from pancreatic islets. Naunyn Schmiedebergs Arch Pharmacol. 1985 May;329(3):299–304. doi: 10.1007/BF00501884. [DOI] [PubMed] [Google Scholar]

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