Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1976 Jul;58(1):230–239. doi: 10.1172/JCI108454

Interactions of acetylcholine and epinephrine on the dynamics of insulin release in vitro.

I M Burr, A E Slonim, R Sharp
PMCID: PMC333174  PMID: 932207

Abstract

An in vitro system for perifusion of rat pancreatic islets has been utilized to define the effects of epinephrine on acetylcholine-induced insulin release over varying concentrations of the two agents. Perifusion of islets with epinephrine before challenge with acetycholine produced marked enhancement of both phases of cholinergically induced insulin release; enhancement of the first phase being more marked with increase in acetylcholine concentration and the converse being observed with the second phase. Perifusion of islets with epinephrine during stimulation with acetylcholine produced inhibition of insulin release, an effect dependent upon the concentration of epinephrine and of acetylcholine. There was an order of difference in the acetycholine concentration needed to overcome significant epinephrine-mediated inhibition of the first phase of insulin release (5 X 10(-4) mug/ml) and that needed to overcome inhibition of the second phase (5 X 10(-3) mug/ml). Comparison of the effects of various concentrations of epinephrine on glucose- and acetyl-choline-induced insulin release revealed that epinephrine was a less potent inhibitor of the first phase of acetylcholine-induced insulin release than of the first phase of glucose-induced insulin release. These data provide some insight into the potential interactions between cholinergic and adrenergic autonomic systems in modifying insulin release.

Full text

PDF
230

Selected References

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

  1. Ahlskog J. E., Hoebel B. G. Overeating and obesity from damage to a noradrenergic system in the brain. Science. 1973 Oct 12;182(4108):166–169. doi: 10.1126/science.182.4108.166. [DOI] [PubMed] [Google Scholar]
  2. Ban T. The septo-preoptico-hypothalamic system and its autonomic function. Prog Brain Res. 1966;21:1–43. doi: 10.1016/s0079-6123(08)62970-2. [DOI] [PubMed] [Google Scholar]
  3. Burns T. W., Mohs J. M., Langley P. E., Yawn R., Chase G. R. Regulation of human lipolysis. In vivo observations on the role of adrenergic receptors. J Clin Invest. 1974 Jan;53(1):338–341. doi: 10.1172/JCI107556. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Burr I. M., Balant L., Stauffacher W., Renold A. E. Adrenergic modification of glucose-induced biphasic insulin release from perifused rat pancreas. Eur J Clin Invest. 1971 Jan;1(4):216–224. doi: 10.1111/eci.1971.1.4.216. [DOI] [PubMed] [Google Scholar]
  5. Burr I. M., Jackson A., Culbert S., Sharp R., Felts P., Olson W. Glucose intolerance and impaired insulin release following 6-hydroxydopamine administration to intact rats. Endocrinology. 1974 Apr;94(4):1072–1076. doi: 10.1210/endo-94-4-1072. [DOI] [PubMed] [Google Scholar]
  6. Burr I. M., Marliss E. B., Stauffacher W., Renold A. E. Diazoxide effects on biphasic insulin release: "adrenergic" suppression and enhancement in the perifused rat pancreas. J Clin Invest. 1971 Jul;50(7):1444–1450. doi: 10.1172/JCI106628. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Burr I. M., Renold A. E., Stauffacher W., Grodsky G. M., Balant L. [Regulation of insulin release in perifused pancreatic tissue]. Acta Diabetol Lat. 1969 Sep;6 (Suppl 1):580–596. [PubMed] [Google Scholar]
  8. Burr I. M., Taft H. P., Stauffacher W., Renold A. E. On the role of cyclic AMP in insulin release: II. Dynamic aspects and relations to adrenergic receptors in the perfused pancreas of adult rats. Ann N Y Acad Sci. 1971 Dec 30;185:245–262. doi: 10.1111/j.1749-6632.1971.tb45253.x. [DOI] [PubMed] [Google Scholar]
  9. Burr I., Hudson W., Page D., Taft H. P. Observations on the effect of a ganglion blocking agent on responses to intravenous glucose infusion. Diabetologia. 1970 Oct;6(5):467–472. doi: 10.1007/BF01211885. [DOI] [PubMed] [Google Scholar]
  10. Burr I., Hudson W., Page D., Taft H. P. The response to intravenous glucose infusion in normal and diabetic subjects. Diabetologia. 1970 Dec;6(6):575–580. doi: 10.1007/BF00418224. [DOI] [PubMed] [Google Scholar]
  11. Cerasi E., Luft R. The effect of an adenosine--3'5'--monophosphate diesterase inhibitor (aminophylline) on the insulin response to glucose infusion in prediabetic and diabetic subjects. Horm Metab Res. 1969 Jul;1(4):162–168. doi: 10.1055/s-0028-1095148. [DOI] [PubMed] [Google Scholar]
  12. Coore H. G., Randle P. J. Regulation of insulin secretion studied with pieces of rabbit pancreas incubated in vitro. Biochem J. 1964 Oct;93(1):66–78. doi: 10.1042/bj0930066. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Debons A. F., Krimsky I., From A., Cloutier R. J. Rapid effects of insulin on the hypothalamic satiety center. Am J Physiol. 1969 Oct;217(4):1114–1118. doi: 10.1152/ajplegacy.1969.217.4.1114. [DOI] [PubMed] [Google Scholar]
  14. Fischer U., Hommel H., Ziegler M., Michael R. The mechanism of insulin secretion after oral glucose administration. I. Multiphasic course of insulin mobilization after oral administration of glucose in conscious dogs. Differences to the behaviour after intravenous administration. Diabetologia. 1972 Apr;8(2):104–110. doi: 10.1007/BF01235634. [DOI] [PubMed] [Google Scholar]
  15. Frohman L. A., Bernardis L. L., Schnatz J. D., Burek L. Plasma insulin and triglyceride levels after hypothalamic lesions in weanling rats. Am J Physiol. 1969 Jun;216(6):1496–1501. doi: 10.1152/ajplegacy.1969.216.6.1496. [DOI] [PubMed] [Google Scholar]
  16. Frohman L. A., Bernardis L. L., Stachura M. E. Factors modifying plasma insulin and glucose responses to ventromedial hypothalamic stimulation. Metabolism. 1974 Nov;23(11):1047–1056. doi: 10.1016/0026-0495(74)90071-7. [DOI] [PubMed] [Google Scholar]
  17. Frohman L. A., Ezdinli E. Z., Javid R. Effect of vagotomy and vagal stimulation on insulin secretion. Diabetes. 1967 Jul;16(7):443–448. doi: 10.2337/diab.16.7.443. [DOI] [PubMed] [Google Scholar]
  18. Fujita Y., Herron A. L., Jr, Seltzer H. S. Confirmation of impaired early insulin response to glycemic stimulus in nonobese mild diabetics. Diabetes. 1975 Jan;24(1):17–27. doi: 10.2337/diab.24.1.17. [DOI] [PubMed] [Google Scholar]
  19. GROSSMAN S. P., GROSSMAN L. FOOD AND WATER INTAKE FOLLOWING LESIONS OR ELECTRICAL STIMULATION OF THE AMYGDALA. Am J Physiol. 1963 Oct;205:761–765. doi: 10.1152/ajplegacy.1963.205.4.761. [DOI] [PubMed] [Google Scholar]
  20. Goldfine I. D., Abraira C., Gruenewald D., Goldstein M. S. Plasma insulin levels during imaginary food ingestion under hypnosis. Proc Soc Exp Biol Med. 1970 Jan;133(1):274–276. doi: 10.3181/00379727-133-34454. [DOI] [PubMed] [Google Scholar]
  21. Goldman J. K., Schnatz J. D., Bernardis L. L., Frohman L. A. Adipose tissue metabolism of weanling rats after destruction of ventromedial hypothalamic nuclei: effect of hypophysectomy and growth hormone. Metabolism. 1970 Nov;19(11):995–1005. doi: 10.1016/0026-0495(70)90046-6. [DOI] [PubMed] [Google Scholar]
  22. Goodner C. J., Koerker D. J., Werbach J. H., Toivola P., Gale C. C. Adrenergic regulation of lipolysis and insulin secretion in the fasted baboon. Am J Physiol. 1973 Mar;224(3):534–539. doi: 10.1152/ajplegacy.1973.224.3.534. [DOI] [PubMed] [Google Scholar]
  23. HALES C. N., RANDLE P. J. Immunoassay of insulin with insulin-antibody precipitate. Biochem J. 1963 Jul;88:137–146. doi: 10.1042/bj0880137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Hommel H., Fischer U., Retzlaff K., Knöfler H. The mechanism of insulin secretion after oral glucose administration. II. Reflex insulin secretion in conscious dogs bearing fistulas of the digestive tract by sham-feeding of glucose or tap water. Diabetologia. 1972 Apr;8(2):111–116. doi: 10.1007/BF01235635. [DOI] [PubMed] [Google Scholar]
  25. Hongslo C. F., Hustvedt B. E., Lovo A. Insulin sensitivity in rats with ventromedial hypothalamic lesions. Acta Physiol Scand. 1974 Apr;90(4):757–763. doi: 10.1111/j.1748-1716.1974.tb05644.x. [DOI] [PubMed] [Google Scholar]
  26. Kaneto A., Kajinuma H., Kosaka K., Nakao K. Stimulation of insulin secretion by parasympathomimetic agents. Endocrinology. 1968 Oct;83(4):651–658. doi: 10.1210/endo-83-4-651. [DOI] [PubMed] [Google Scholar]
  27. Kaneto A., Kosaka K., Nakao K. Effects of stimulation of the vagus nerve on insulin secretion. Endocrinology. 1967 Mar;80(3):530–536. doi: 10.1210/endo-80-3-530. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Leibowitz S. F. Hypothalamic alpha- and beta-adrenergic systems regulate both thirst and hunger in the rat. Proc Natl Acad Sci U S A. 1971 Feb;68(2):332–334. doi: 10.1073/pnas.68.2.332. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Lerner R. L., Porte D., Jr Relationship between intravenous glucose loads, insulin responses and glucose disappearance rate. J Clin Endocrinol Metab. 1971 Sep;33(3):409–417. doi: 10.1210/jcem-33-3-409. [DOI] [PubMed] [Google Scholar]
  31. Lowrie E. G., Soeldner J. S., Hampers C. L., Merrill J. P. Glucose metabolism and insulin secretion in uremic, prediabetic, and normal subjects. J Lab Clin Med. 1970 Oct;76(4):603–615. [PubMed] [Google Scholar]
  32. MORGANE P. J. Alterations in feeding and drinking behavior of rats with lesions in globi pallidi. Am J Physiol. 1961 Sep;201:420–428. doi: 10.1152/ajplegacy.1961.201.3.420. [DOI] [PubMed] [Google Scholar]
  33. Malaisse W., Malaisse-Lagae F., Wright P. H., Ashmore J. Effects of adrenergic and cholinergic agents upon insulin secretion in vitro. Endocrinology. 1967 May;80(5):975–978. doi: 10.1210/endo-80-5-975. [DOI] [PubMed] [Google Scholar]
  34. Margules D. L. Alpha-adrenergic receptors in hypothalamus for the suppression of feeding behavior by satiety. J Comp Physiol Psychol. 1970 Oct;73(1):1–12. doi: 10.1037/h0030007. [DOI] [PubMed] [Google Scholar]
  35. Marshall J. F., Teitelbaum P. A comparison of the eating in response to hypothermic and glucoprivic challenges after nigral 6-hydroxydopamine and lateral hypothalamic electrolytic lesions in rats. Brain Res. 1973 May 30;55(1):229–233. doi: 10.1016/0006-8993(73)90507-6. [DOI] [PubMed] [Google Scholar]
  36. Martin J. M., Konijnendijk W., Bouman P. R. Insulin and growth hormone secretion in rats with ventromedial hypothalamic lesions maintained on restricted food intake. Diabetes. 1974 Mar;23(3):203–208. doi: 10.2337/diab.23.3.203. [DOI] [PubMed] [Google Scholar]
  37. Montague W., Cook J. R. The role of adenosine 3':5'-cyclic monophosphate in the regulation of insulin release by isolated rat islets of Langerhans. Biochem J. 1971 Mar;122(1):115–120. doi: 10.1042/bj1220115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Müller E. E., Frohman L. A., Cocchi D. Drug control of hyperglycemia and inhibition of insulin secretion due to centrally administered 2-deoxy-D-glucose. Am J Physiol. 1973 May;224(5):1210–1217. doi: 10.1152/ajplegacy.1973.224.5.1210. [DOI] [PubMed] [Google Scholar]
  39. Niijima A. An electrophysiological study on the regulatory mechanism of blood sugar level in the rabbit. Brain Res. 1975 Apr 11;87(2-3):195–199. doi: 10.1016/0006-8993(75)90416-3. [DOI] [PubMed] [Google Scholar]
  40. Oomura Y. Central mechanism of feeding. Adv Biophys. 1973;5(0):65–142. [PubMed] [Google Scholar]
  41. 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]
  42. Porte D., Jr, Graber A. L., Kuzuya T., Williams R. H. The effect of epinephrine on immunoreactive insulin levels in man. J Clin Invest. 1966 Feb;45(2):228–236. doi: 10.1172/JCI105335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Porte D., Jr, Robertson R. P. Control of insulin secretion by catecholamines, stress, and the sympathetic nervous system. Fed Proc. 1973 Jul;32(7):1792–1796. [PubMed] [Google Scholar]
  44. SAMOLS E., MARKS V. INTERPRETATION OF THE INTRAVENOUS GLUCOSE TEST. Lancet. 1965 Feb 27;1(7383):462–463. doi: 10.1016/s0140-6736(65)91592-8. [DOI] [PubMed] [Google Scholar]
  45. SCHREINER L., RIOCH D. M., PECHTEL C., MASSERMAN J. H. Behavioral changes following thalamic injury in cat. J Neurophysiol. 1953 May;16(3):234–246. doi: 10.1152/jn.1953.16.3.234. [DOI] [PubMed] [Google Scholar]
  46. Schnatz J. D., Frohman L. A., Bernardis L. L. The effect of lateral hypothalamic lesions in weanling rats bearing lesions in the ventromedial hypothalamic nuclei. Proc Soc Exp Biol Med. 1973 Jan;142(1):256–257. doi: 10.3181/00379727-142-37000. [DOI] [PubMed] [Google Scholar]
  47. Seltzer H. S., Allen E. W., Herron A. L., Jr, Brennan M. T. Insulin secretion in response to glycemic stimulus: relation of delayed initial release to carbohydrate intolerance in mild diabetes mellitus. J Clin Invest. 1967 Mar;46(3):323–335. doi: 10.1172/JCI105534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Sharp R., Culbert S., Cook J., Jennings A., Burr I. M. Cholinergic modification of glucose-induced biphasic insulin release in vitro. J Clin Invest. 1974 Mar;53(3):710–716. doi: 10.1172/JCI107609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Shimazu T., Ogasawara S. Effects of hypothalamic stimulation on gluconeogenesis and glycolysis in rat liver. Am J Physiol. 1975 Jun;228(6):1787–1793. doi: 10.1152/ajplegacy.1975.228.6.1787. [DOI] [PubMed] [Google Scholar]
  50. Simpson R. G., Benedetti A., Grodsky G. M., Karam J. H., Forsham P. H. Stimulation of insulin release by glucagon in noninsulin-dependent diabetics. Metabolism. 1966 Nov;15(11):1046–1049. doi: 10.1016/0026-0495(66)90055-2. [DOI] [PubMed] [Google Scholar]
  51. Thorell J. I. Effect of transient elevation of plasma insulin within physiologic levels (simulated early insulin response) on blood glucose. J Clin Endocrinol Metab. 1973 Sep;37(3):423–430. doi: 10.1210/jcem-37-3-423. [DOI] [PubMed] [Google Scholar]
  52. Ungerstedt U. Adipsia and aphagia after 6-hydroxydopamine induced degeneration of the nigro-striatal dopamine system. Acta Physiol Scand Suppl. 1971;367:95–122. doi: 10.1111/j.1365-201x.1971.tb11001.x. [DOI] [PubMed] [Google Scholar]
  53. Woods S. C. Conditioned hypoglycemia: effect of vagotomy and pharmacological blockade. Am J Physiol. 1972 Dec;223(6):1424–1427. doi: 10.1152/ajplegacy.1972.223.6.1424. [DOI] [PubMed] [Google Scholar]
  54. Woods S. C., Porte D., Jr Neural control of the endocrine pancreas. Physiol Rev. 1974 Jul;54(3):596–619. doi: 10.1152/physrev.1974.54.3.596. [DOI] [PubMed] [Google Scholar]
  55. 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]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES