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The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1984 Jan;73(1):216–223. doi: 10.1172/JCI111194

Contribution of the pancreas to circulating somatostatin-like immunoreactivity in the normal dog.

G J Taborsky Jr, J W Ensinck
PMCID: PMC425002  PMID: 6140271

Abstract

These studies were performed to assess the contribution of the pancreas to the somatostatin-like immunoreactivity (SLI) circulating in arterial and portal venous plasma. Basal SLI concentrations in arterial, pancreatic venous, and portal venous plasma were 95 +/- 9, 277 +/- 32, and 130 +/- 12 pg/ml, (means +/- SEM), respectively. Measurement of pancreatic and portal venous blood flow (5 +/- 1 vs. 365 +/- 46 ml/min) and hematocrit allowed calculation of net, base-line SLI output from the right lobe of the pancreas (521 +/- 104 pg/min) and from the gastrointestinal tract (8,088 +/- 1,487 pg/min), which suggested that the contribution of the pancreas to circulating SLI was minor when the D cells were not stimulated. To stimulate the secretion of SLI from both pancreatic and nonpancreatic sources, isoproterenol, a beta-adrenergic agonist, was infused intravenously for 1 h into six anesthetized dogs. Arterial SLI increased by 52 +/- 9 pg/ml; superior pancreatico-duodenal venous SLI increased by 380 +/- 95 pg/ml; portal venous SLI increased by 134 +/- 14 pg/ml. Pancreatic venous blood flow remained unchanged at 5 +/- 1 ml/min, but portal venous blood flow increased to 522 +/- 62 ml/min. SLI output from the right lobe of the pancreas increased by 684 +/- 227 pg/min and that from the gastrointestinal tract increased by 23,911 +/- 3,197 pg/min, again suggesting that the pancreas was a minor source of circulating SLI even when the D cells were stimulated. We conclude that the measurement of arterial-venous SLI concentrations, in the absence of measurements of organ blood flow, can give a false impression of the organ's contributions of circulating SLI. To verify that the contribution of the pancreas was negligible, six dogs received an acute pancreatectomy and then an intravenous infusion of isoproterenol at the same rate. In these dogs, both the base-line level of SLI in arterial plasma (109 +/- 12 pg/ml) and the increment during isoproterenol (56 +/- 8 pg/ml) were similar to those of normal dogs. Likewise, in pancreatectomized dogs both the base-line level of SLI in portal venous plasma (129 +/- 16 pg/ml) and the increment during isoproterenol (174 +/- 34 pg/ml) were similar to those of normal dogs. We conclude that, in normal dogs, the pancreas makes a negligible contribution to the basal and stimulated level of SLI in arterial and portal venous plasma and therefore that these levels should not be used as an index of secretory activity of the pancreatic D cells.

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Selected References

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

  1. Arimura A., Sato H., Dupont A., Nishi N., Schally A. V. Somatostatin: abundance of immunoreactive hormone in rat stomach and pancreas. Science. 1975 Sep 19;189(4207):1007–1009. doi: 10.1126/science.56779. [DOI] [PubMed] [Google Scholar]
  2. Boden G., Master R. W., Sattler M. A., Martin J. S., Tansy M. F., Owen O. E. Adrenergic control of somatostatin release. Endocrinology. 1982 Oct;111(4):1166–1172. doi: 10.1210/endo-111-4-1166. [DOI] [PubMed] [Google Scholar]
  3. Bonner-Weir S., Orci L. New perspectives on the microvasculature of the islets of Langerhans in the rat. Diabetes. 1982 Oct;31(10):883–889. doi: 10.2337/diab.31.10.883. [DOI] [PubMed] [Google Scholar]
  4. Chayvialle J. A., Rayford P. L., Thompson J. C. Radioimmunoassay study of hepatic clearance and disappearance half-time of somatostatin and vasoactive intestinal peptide in dogs. Gut. 1981 Sep;22(9):732–737. doi: 10.1136/gut.22.9.732. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chiba T., Kadowaki S., Taminato T., Abe H., Chihara K., Matsukura S., Goto Y., Seino Y., Fujita T. Concentration and secretion of gastric somatostatin in streptozotocin-diabetic rats. Diabetes. 1981 Mar;30(3):188–191. doi: 10.2337/diab.30.3.188. [DOI] [PubMed] [Google Scholar]
  6. Chiba T., Taminato T., Kadowaki S., Chihara K., Matsukura S., Nozawa M., Seino Y., Fujita T. Reversal of increased gastric somatostatin in streptozotocin-diabetic rats by whole pancreas transplantation. Diabetes. 1981 Sep;30(9):724–727. doi: 10.2337/diab.30.9.724. [DOI] [PubMed] [Google Scholar]
  7. Conlon J. M., Bridgeman M., Alberti K. G. The nature of big plasma somatostatin: implications for the measurement of somatostatin-like immunoreactivity in human plasma. Anal Biochem. 1982 Sep 15;125(2):243–252. doi: 10.1016/0003-2697(82)90002-1. [DOI] [PubMed] [Google Scholar]
  8. Dubois M. P. Immunoreactive somatostatin is present in discrete cells of the endocrine pancreas. Proc Natl Acad Sci U S A. 1975 Apr;72(4):1340–1343. doi: 10.1073/pnas.72.4.1340. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gersell D. J., Gingerich R. L., Greider M. H. Regional distribution and concentration of pancreatic polypeptide in the human and canine pancreas. Diabetes. 1979 Jan;28(1):11–15. [PubMed] [Google Scholar]
  10. Hermansen K. Characterisation of the abnormal pancreatic D and A cell function in streptozotocin diabetic dogs: studies with D-glyceraldehyde, dihydroxyacetone, D-mannoheptulose, D-glucose, and L-arginine. Diabetologia. 1981 Nov;21(5):489–494. doi: 10.1007/BF00257791. [DOI] [PubMed] [Google Scholar]
  11. Ipp E., Dobbs R. E., Harris V., Arimura A., Vale W., Unger R. H. The effects of gastrin, gastric inhibitory polypeptide, secretin, and the octapeptide of cholecystokinin upon immunoreactive somatostatin release by the perfused canine pancreas. J Clin Invest. 1977 Nov;60(5):1216–1219. doi: 10.1172/JCI108875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Jaspan J., Polonsky K., Lewis M., Moossa A. R. Reduction in portal vein blood flow by somatostatin. Diabetes. 1979 Oct;28(10):888–892. doi: 10.2337/diab.28.10.888. [DOI] [PubMed] [Google Scholar]
  13. Kadowaki S., Taminato T., Chiba T., Goto Y., Nozawa M., Seino Y., Matsukura S., Fujita T. Reversal of the enhanced somatostatin release from the isolated, perfused diabetic rat pancreas after the amelioration of diabetes by whole pancreas transplantation. Diabetes. 1980 Sep;29(9):742–746. doi: 10.2337/diab.29.9.742. [DOI] [PubMed] [Google Scholar]
  14. Kadowaki S., Taminato T., Chiba T., Goto Y., Nozawa M., Seino Y., Matsukura S., Fujita T. Somatostatin release from the isolated, perfused diabetic rat pancreas: inverse relationship between pancreatic somatostatin and insulin. Diabetes. 1980 Dec;29(12):960–963. doi: 10.2337/diab.29.12.960. [DOI] [PubMed] [Google Scholar]
  15. Kawai K., Orci L., Unger R. H. High somatostatin uptake by the isolated perfused dog pancreas consistent with "insulo-acinar" axis. Endocrinology. 1982 Feb;110(2):660–662. doi: 10.1210/endo-110-2-660. [DOI] [PubMed] [Google Scholar]
  16. Kazumi T., Utsumi M., Yoshino G., Ishihara K., Hirose Y., Makimura H., Baba S. Somatostatin concentration responds to arginine in portal plasma: effects of fasting, streptozotocin diabetes, and insulin administration in diabetic rats. Diabetes. 1980 Jan;29(1):71–73. doi: 10.2337/diab.29.1.71. [DOI] [PubMed] [Google Scholar]
  17. Konturek S. J. Current concepts of neuro-hormonal control of pancreatic secretion. Ir J Med Sci. 1978 Jan;147(1):1–10. doi: 10.1007/BF02939360. [DOI] [PubMed] [Google Scholar]
  18. Lifson N., Kramlinger K. G., Mayrand R. R., Lender E. J. Blood flow to the rabbit pancreas with special reference to the islets of Langerhans. Gastroenterology. 1980 Sep;79(3):466–473. [PubMed] [Google Scholar]
  19. McIntosh C., Arnold R., Bothe E., Becker H., Köbberling J., Creutzfeldt W. Gastrointestinal somatostatin: extraction and radioimmunoassay in different species. Gut. 1978 Jul;19(7):655–663. doi: 10.1136/gut.19.7.655. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Noe B. D. Synthesis of one form of pancreatic islet somatostatin predominates. J Biol Chem. 1981 Sep 25;256(18):9397–9400. [PubMed] [Google Scholar]
  21. Patel Y. C., Cameron D. P., Bankier A., Malaisse-Lagae F., Ravazzola M., Studer P., Orci L. Changes in somatostatin concentration in pancreas and other tissues of streptozotocin diabetic rats. Endocrinology. 1978 Sep;103(3):917–923. doi: 10.1210/endo-103-3-917. [DOI] [PubMed] [Google Scholar]
  22. Patel Y. C., Wheatley T., Ning C. Multiple forms of immunoreactive somatostatin: comparison of distribution in neural and nonneural tissues and portal plasma of the rat. Endocrinology. 1981 Dec;109(6):1943–1949. doi: 10.1210/endo-109-6-1943. [DOI] [PubMed] [Google Scholar]
  23. Patel Y. C., Wheatley T., Zingg H. H. Increased blood somatostatin concentration in streptozotocin diabetic rats. Life Sci. 1980 Oct 27;27(17):1563–1570. doi: 10.1016/0024-3205(80)90565-2. [DOI] [PubMed] [Google Scholar]
  24. Polonsky K. S., Jaspan J. B., Berelowitz M., Emmanouel D. S., Dhorajiwala J. Hepatic and renal metabolism of somatostatin-like immunoreactivity. Simultaneous assessment in the dog. J Clin Invest. 1981 Nov;68(5):1149–1157. doi: 10.1172/JCI110359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. Sacks H., Terry L. C. Clearance of immunoreactive somatostatin by perfused rat liver. J Clin Invest. 1981 Feb;67(2):419–429. doi: 10.1172/JCI110050. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. 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]
  28. Schusdziarra V., Dobbs R. E., Harris V., Unger R. H. Immunoreactive somatostatin levels in plasma of normal and alloxan diabetic dogs. FEBS Lett. 1977 Sep 1;81(1):69–72. doi: 10.1016/0014-5793(77)80930-7. [DOI] [PubMed] [Google Scholar]
  29. Schusdziarra V., Harris V., Conlon J. M., Arimura A., Unger R. Pancreatic and gastric somatostatin release in response to intragastric and intraduodenal nutrients and HCl in the dog. J Clin Invest. 1978 Sep;62(3):509–518. doi: 10.1172/JCI109154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Schusdziarra V., Harris V., Unger R. H. Half-life of somatostatin-like immunoreactivity in canine plasma. Endocrinology. 1979 Jan;104(1):109–110. doi: 10.1210/endo-104-1-109. [DOI] [PubMed] [Google Scholar]
  31. Schusdziarra V., Rouiller D., Harris V., Unger R. H. Origin of peripheral venous hypersomatostatinemia in alloxan-diabetic dogs. Endocrinology. 1981 Oct;109(4):1107–1116. doi: 10.1210/endo-109-4-1107. [DOI] [PubMed] [Google Scholar]
  32. Schusdziarra V., Rouiller D., Harris V., Unger R. H. Plasma somatostatin-like immunoreactivity in depancreatized dogs. Endocrinology. 1979 Sep;105(3):595–599. doi: 10.1210/endo-105-3-595. [DOI] [PubMed] [Google Scholar]
  33. Schusdziarra V., Rouiller D., Pietri A., Harris V., Zyznar E., Conlon J. M., Unger R. H. Pancreatic and gastric release of somatostatinlike immunoreactivity during intestinal phase of a meal. Am J Physiol. 1979 Dec;237(6):E555–E560. doi: 10.1152/ajpendo.1979.237.6.E555. [DOI] [PubMed] [Google Scholar]
  34. Shoelson S., Polonsky K., Docherty H., Jaspan J., Rubenstein A. Evidence for the presence of somatostatin 28 in plasma. Diabetes. 1982 May;31(5 Pt 1):474–477. doi: 10.2337/diab.31.5.474. [DOI] [PubMed] [Google Scholar]
  35. Taborsky G. J., Jr, Ensinck J. W. Extraction of somatostatin by the pancreas. Endocrinology. 1983 Jan;112(1):303–307. doi: 10.1210/endo-112-1-303. [DOI] [PubMed] [Google Scholar]
  36. Taborsky G. J., Jr, Smith P. H., Porte D., Jr Differential effects of somatostatin analogues on alpha- and beta-cells of the pancreas. Am J Physiol. 1979 Feb;236(2):E123–E128. doi: 10.1152/ajpendo.1979.236.2.E123. [DOI] [PubMed] [Google Scholar]
  37. Trent D. F., Weir G. C. Heterogeneity of somatostatin-like peptides in rat brain, pancreas, and gastrointestinal tract. Endocrinology. 1981 Jun;108(6):2033–2038. doi: 10.1210/endo-108-6-2033. [DOI] [PubMed] [Google Scholar]
  38. Trimble E. R., Gerber P. P., Renold A. E. Abnormalities of pancreatic somatostatin secretion corrected by in vivo insulin treatment of streptozotocin-diabetic rats. Diabetes. 1981 Oct;30(10):865–867. doi: 10.2337/diab.30.10.865. [DOI] [PubMed] [Google Scholar]
  39. de Haën C., Little S. A., May J. M., Williams R. H. Characterization of proinsulin-insulin intermediates in human plasma. J Clin Invest. 1978 Oct;62(4):727–737. doi: 10.1172/JCI109183. [DOI] [PMC free article] [PubMed] [Google Scholar]

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