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. 1988 Nov;82(5):1538–1545. doi: 10.1172/JCI113763

Pancreatic noradrenergic nerves are activated by neuroglucopenia but not by hypotension or hypoxia in the dog. Evidence for stress-specific and regionally selective activation of the sympathetic nervous system.

P J Havel 1, R C Veith 1, B E Dunning 1, G J Taborsky Jr 1
PMCID: PMC442720  PMID: 3183052

Abstract

To determine if acute stress activates pancreatic noradrenergic nerves, pancreatic norepinephrine (NE) output (spillover) was measured in halothane-anesthetized dogs. Central neuroglucopenia, induced by intravenous 2-deoxy-D-glucose [( 2-DG] 600 mg/kg + 13.5 mg/kg-1 per min-1) increased pancreatic NE output from a baseline of 380 +/- 100 to 1,490 +/- 340 pg/min (delta = +1,110 +/- 290 pg/min, P less than 0.01). Surgical denervation of the pancreas reduced this response by 90% (delta = +120 +/- 50 pg/min, P less than 0.01 vs. intact innervation), suggesting that 2-DG activated pancreatic nerves by increasing the central sympathetic outflow to the pancreas rather than by acting directly on nerves within the pancreas itself. These experiments provide the first direct evidence of stress-induced activation of pancreatic noradrenergic nerves in vivo. In contrast, neither hemorrhagic hypotension (50 mmHg) nor hypoxia (6-8% O2) increased pancreatic NE output (delta = +80 +/- 110 and -20 +/- 60 pg/min, respectively, P less than 0.01 vs. neuroglucopenia) despite both producing increases of arterial plasma NE and epinephrine similar to glucopenia. The activation of pancreatic noradrenergic nerves is thus stress specific. Furthermore, because both glucopenia and hypotension increased arterial NE, yet only glucopenia activated pancreatic nerves, it is suggested that a regionally selective pattern of sympathetic activation can be elicited by acute stress, a condition in which sympathetic activation has traditionally been thought to be generalized and nondiscrete.

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Selected References

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  1. Ahrén B., Dunning B. E., Havel P. J., Veith R. C., Taborsky G. J., Jr Extraction of epinephrine and norepinephrine by the dog pancreas in vivo. Metabolism. 1988 Jan;37(1):68–73. doi: 10.1016/0026-0495(88)90031-5. [DOI] [PubMed] [Google Scholar]
  2. Ahrén B., Taborsky G. J., Jr, Porte D., Jr Neuropeptidergic versus cholinergic and adrenergic regulation of islet hormone secretion. Diabetologia. 1986 Dec;29(12):827–836. doi: 10.1007/BF00870137. [DOI] [PubMed] [Google Scholar]
  3. Ahrén B., Veith R. C., Taborsky G. J., Jr Sympathetic nerve stimulation versus pancreatic norepinephrine infusion in the dog: 1). Effects on basal release of insulin and glucagon. Endocrinology. 1987 Jul;121(1):323–331. doi: 10.1210/endo-121-1-323. [DOI] [PubMed] [Google Scholar]
  4. BROWN J. Effects of 2-deoxyglucose on carbohydrate metablism: review of the literature and studies in the rat. Metabolism. 1962 Oct;11:1098–1112. [PubMed] [Google Scholar]
  5. Best J. D., Taborsky G. J., Jr, Flatness D. E., Halter J. B. Effect of pentobarbital anesthesia on plasma norepinephrine kinetics in dogs. Endocrinology. 1984 Sep;115(3):853–857. doi: 10.1210/endo-115-3-853. [DOI] [PubMed] [Google Scholar]
  6. Cherrington A. D., Chiasson J. L., Liljenquist J. E., Jennings A. S., Keller U., Lacy W. W. The role of insulin and glucagon in the regulation of basal glucose production in the postabsorptive dog. J Clin Invest. 1976 Dec;58(6):1407–1418. doi: 10.1172/JCI108596. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Christensen N. J., Iversen J. Release of large amounts of noradrenaline from the isolated perfused canine pancreas during glucose deprivation. Diabetologia. 1973 Oct;9(5):396–399. doi: 10.1007/BF01239435. [DOI] [PubMed] [Google Scholar]
  8. Esler M., Jennings G., Korner P., Blombery P., Sacharias N., Leonard P. Measurement of total and organ-specific norepinephrine kinetics in humans. Am J Physiol. 1984 Jul;247(1 Pt 1):E21–E28. doi: 10.1152/ajpendo.1984.247.1.E21. [DOI] [PubMed] [Google Scholar]
  9. Esler M., Jennings G., Korner P., Willett I., Dudley F., Hasking G., Anderson W., Lambert G. Assessment of human sympathetic nervous system activity from measurements of norepinephrine turnover. Hypertension. 1988 Jan;11(1):3–20. doi: 10.1161/01.hyp.11.1.3. [DOI] [PubMed] [Google Scholar]
  10. Evans M. I., Halter J. B., Porte D., Jr Comparison of double- and single-isotope enzymatic derivative methods for measuring catecholamines in human plasma. Clin Chem. 1978 Apr;24(4):567–570. [PubMed] [Google Scholar]
  11. Folkow B. Plasma catecholamines as markers for sympatho-adrenal activity in man. Introductory remarks. Acta Physiol Scand Suppl. 1984;527:7–9. [PubMed] [Google Scholar]
  12. Frohman L. A., Muller E. E., Cocchi D. Central nervous system mediated inhibition of insulin secretion due to 2-deoxyglucose. Horm Metab Res. 1973 Jan;5(1):21–26. doi: 10.1055/s-0028-1093995. [DOI] [PubMed] [Google Scholar]
  13. Frohman L. A., Nagai K. Central nervous system-mediated stimulation of glucagon secretion in the dog following 2-deoxyglucose. Metabolism. 1976 Nov;25(11 Suppl 1):1449–1452. doi: 10.1016/s0026-0495(76)80162-x. [DOI] [PubMed] [Google Scholar]
  14. Havel P. J., Flatness D. E., Halter J. B., Best J. D., Veith R. C., Taborsky G. J., Jr Halothane anesthesia does not suppress sympathetic activation produced by neuroglucopenia. Am J Physiol. 1987 May;252(5 Pt 1):E667–E672. doi: 10.1152/ajpendo.1987.252.5.E667. [DOI] [PubMed] [Google Scholar]
  15. Hisatomi A., Maruyama H., Orci L., Vasko M., Unger R. H. Adrenergically mediated intrapancreatic control of the glucagon response to glucopenia in the isolated rat pancreas. J Clin Invest. 1985 Feb;75(2):420–426. doi: 10.1172/JCI111716. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hjemdahl P., Freyschuss U., Juhlin-Dannfelt A., Linde B. Differentiated sympathetic activation during mental stress evoked by the Stroop test. Acta Physiol Scand Suppl. 1984;527:25–29. [PubMed] [Google Scholar]
  17. 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]
  18. Järhult J., Holst J. J. Reflex adrenergic control of endocrine pancreas evoked by unloading of carotid baroreceptors in cats. Acta Physiol Scand. 1978 Oct;104(2):188–202. doi: 10.1111/j.1748-1716.1978.tb06266.x. [DOI] [PubMed] [Google Scholar]
  19. Khalil Z., Marley P. D., Livett B. G. Elevation in plasma catecholamines in response to insulin stress is under both neuronal and nonneuronal control. Endocrinology. 1986 Jul;119(1):159–167. doi: 10.1210/endo-119-1-159. [DOI] [PubMed] [Google Scholar]
  20. MILLAR R. A., KEENER E. B., BENFEY B. G. Plasma adrenaline and noradrenaline after phenoxybenzamine administration, and during haemorrhagic hypotension, in normal and adrenalectomized dogs. Br J Pharmacol Chemother. 1959 Mar;14(1):9–13. doi: 10.1111/j.1476-5381.1959.tb00921.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Marliss E. B., Girardier L., Seydoux J., Wollheim C. B., Kanazawa Y., Orci L., Renold A. E., Porte D., Jr Glucagon release induced by pancreatic nerve stimulation in the dog. J Clin Invest. 1973 May;52(5):1246–1259. doi: 10.1172/JCI107292. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. Porte D., Jr, Girardier L., Seydoux J., Kanazawa Y., Posternak J. Neural regulation of insulin secretion in the dog. J Clin Invest. 1973 Jan;52(1):210–214. doi: 10.1172/JCI107168. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rappaport E. B., Young J. B., Landsberg L. Effects of 2-deoxy-D-glucose on the cardiac sympathetic nerves and the adrenal medulla in the rat: further evidence for a dissociation of sympathetic nervous system and adrenal medullary responses. Endocrinology. 1982 Feb;110(2):650–656. doi: 10.1210/endo-110-2-650. [DOI] [PubMed] [Google Scholar]
  25. Taborsky G. J., Jr, Halter J. B., Baum D., Best J. D., Porte D., Jr Pentobarbital anesthesia suppresses basal and 2-deoxy-D-glucose-stimulated plasma catecholamines. Am J Physiol. 1984 Nov;247(5 Pt 2):R905–R910. doi: 10.1152/ajpregu.1984.247.5.R905. [DOI] [PubMed] [Google Scholar]
  26. Young J. B., Landsberg L. Effect of diet and cold exposure on norepinephrine turnover in pancreas and liver. Am J Physiol. 1979 May;236(5):E524–E533. doi: 10.1152/ajpendo.1979.236.5.E524. [DOI] [PubMed] [Google Scholar]
  27. Young J. B., Rosa R. M., Landsberg L. Dissociation of sympathetic nervous system and adrenal medullary responses. Am J Physiol. 1984 Jul;247(1 Pt 1):E35–E40. doi: 10.1152/ajpendo.1984.247.1.E35. [DOI] [PubMed] [Google Scholar]
  28. Zimpfer M., Manders W. T., Barger A. C., Vatner S. F. Pentobarbital alters compensatory neural and humoral mechanisms in response to hemorrhage. Am J Physiol. 1982 Nov;243(5):H713–H721. doi: 10.1152/ajpheart.1982.243.5.H713. [DOI] [PubMed] [Google Scholar]

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