Abstract
Prosomatostatin (pro-S) and its bioactive posttranslational products, somatostatin-14 (S-14), somatostatin-13 (S-13), and somatostatin-28 (S-28), were measured in human plasma by the use of immunoglobulins to the NH2-terminus of S-28 conjugated with agarose to separate them and, thereafter, by RIA with an antiserum recognizing the COOH-terminus of pro-S, and by specific RIA for the NH2-terminus of S-14 and pro-S. In healthy men, mean basal levels of pro-S were 4 pg equivalent S-14/ml; S-14/S-13 combined were 9 pg equivalent S-14/ml; and S-28 levels were 16 pg/ml. After a 700-kcal meal, pro-S, S-14, and S-14/S-13 did not change, whereas S-28 levels doubled by 120 min and remained elevated for 240 min. To evaluate the origins of these peptides, their levels were compared in peripheral, portal, gastric, and mesenteric veins of anesthetized patients and in patients with total resection of stomach and pancreas before and after nutrient intake. The stomach and small intestine were sources of both peptides; however, most S-28 originated in the small intestine. These findings suggest that, in contrast to S-14, S-28 is a hormone and may modulate postprandial nutrient absorption and use.
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- Amherdt M., Patel Y. C., Orci L. Selective binding of somatostatin-14 and somatostatin-28 to islet cells revealed by quantitative electron microscopic autoradiography. J Clin Invest. 1987 Nov;80(5):1455–1458. doi: 10.1172/JCI113225. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Aron D. C., Andrews P. C., Dixon J. E., Roos B. A. Identification of cellular prosomatostatin and nonsomatostatin peptides derived from its amino terminus. Biochem Biophys Res Commun. 1984 Oct 30;124(2):450–456. doi: 10.1016/0006-291x(84)91574-2. [DOI] [PubMed] [Google Scholar]
- BEHAL F. J., HAMILTON R. D., DAWSON F. B., TERRELL L. C. A STUDY OF THE ACTIVITY OF HUMAN PLASMA AMINOPEPTIDASE COMPONENTS ON DIPEPTIDES AND CHROMOGENIC SUBSTRATES. Arch Biochem Biophys. 1964 Nov;108:207–214. doi: 10.1016/0003-9861(64)90377-7. [DOI] [PubMed] [Google Scholar]
- Baldissera F. G., Munoz-Perez M. A., Holst J. J. Somatostatin 1-28 circulates in human plasma. Regul Pept. 1983 Apr;6(1):63–69. doi: 10.1016/0167-0115(83)90135-0. [DOI] [PubMed] [Google Scholar]
- Baskin D. G., Ensinck J. W. Somatostatin in epithelial cells of intestinal mucosa is present primarily as somatostatin 28. Peptides. 1984 May-Jun;5(3):615–621. doi: 10.1016/0196-9781(84)90092-5. [DOI] [PubMed] [Google Scholar]
- 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]
- Chayvialle J. A., Miyata M., Rayford P. L., Thompson J. C. Effects of test meal, intragastric nutrients, and intraduodenal bile on plasma concentrations of immunoreactive somatostatin and vasoactive intestinal peptide in dogs. Gastroenterology. 1980 Nov;79(5 Pt 1):844–852. [PubMed] [Google Scholar]
- Chiba T., Park J., Yamada T. Biosynthesis of somatostatin in canine fundic D cells. J Clin Invest. 1988 Feb;81(2):282–287. doi: 10.1172/JCI113319. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Hales J. R., Rowell L. B., King R. B. Regional distribution of blood flow in awake heat-stressed baboons. Am J Physiol. 1979 Dec;237(6):H705–H712. doi: 10.1152/ajpheart.1979.237.6.H705. [DOI] [PubMed] [Google Scholar]
- Hilsted L., Holst J. J. On the accuracy of radioimmunological determination of somatostatin in plasma. Regul Pept. 1982 Jun;4(1):13–31. doi: 10.1016/0167-0115(82)90105-7. [DOI] [PubMed] [Google Scholar]
- Johansson O., Hökfelt T., Elde R. P. Immunohistochemical distribution of somatostatin-like immunoreactivity in the central nervous system of the adult rat. Neuroscience. 1984 Oct;13(2):265–339. doi: 10.1016/0306-4522(84)90233-1. [DOI] [PubMed] [Google Scholar]
- Konturek S. J., Kwiecień N., Obtułowicz W., Bielański W., Oleksy J., Schally A. V. Effects of somatostatin-14 and somatostatin-28 on plasma hormonal and gastric secretory responses to cephalic and gastrointestinal stimulation in man. Scand J Gastroenterol. 1985 Jan;20(1):31–38. doi: 10.3109/00365528509089629. [DOI] [PubMed] [Google Scholar]
- Kronheim S., Berelowitz M., Pimstone B. L. The characterization of somatostatin-like immunoreactivity in human serum. Diabetes. 1978 May;27(5):523–529. doi: 10.2337/diab.27.5.523. [DOI] [PubMed] [Google Scholar]
- Mandarino L., Stenner D., Blanchard W., Nissen S., Gerich J., Ling N., Brazeau P., Bohlen P., Esch F., Guillemin R. Selective effects of somatostatin-14, -25 and -28 on in vitro insulin and glucagon secretion. Nature. 1981 May 7;291(5810):76–77. doi: 10.1038/291076a0. [DOI] [PubMed] [Google Scholar]
- Marre M., Miller J., Helman A. M., Assan R. Reciprocal gastropancreatic modulations for the release of somatostatin-like immunoreactivity, glucagon, and insulin in the rat. Diabetes. 1983 Aug;32(8):768–773. doi: 10.2337/diab.32.8.768. [DOI] [PubMed] [Google Scholar]
- McIntosh C. H. Gastrointestinal somatostatin: distribution, secretion and physiological significance. Life Sci. 1985 Dec 2;37(22):2043–2058. doi: 10.1016/0024-3205(85)90576-4. [DOI] [PubMed] [Google Scholar]
- Millar R. P., Sheward W. J., Wegener I., Fink G. Somatostatin-28 is an hormonally active peptide secreted into hypophysial portal vessel blood. Brain Res. 1983 Feb 7;260(2):334–337. doi: 10.1016/0006-8993(83)90692-3. [DOI] [PubMed] [Google Scholar]
- Patel Y. C. A high molecular weight form of somatostatin-28 (1-12)-like immunoreactive substance without somatostatin-14 immunoreactivity in the rat pancreas. Evidence that somatostatin-14 synthesis can occur independently of somatostatin-28. J Clin Invest. 1983 Dec;72(6):2137–2143. doi: 10.1172/JCI111178. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Patel Y. C., Reichlin S. Somatostatin in hypothalamus, extrahypothalamic brain, and peripheral tissues of the rat. Endocrinology. 1978 Feb;102(2):523–530. doi: 10.1210/endo-102-2-523. [DOI] [PubMed] [Google Scholar]
- Patel Y. C., Wheatley T., Fitz-Patrick D., Brock G. A sensitive radioimmunoassay for immunoreactive somatostatin in extracted plasma: measurement and characterization of portal and peripheral plasma in the rat. Endocrinology. 1980 Jul;107(1):306–313. doi: 10.1210/endo-107-1-306. [DOI] [PubMed] [Google Scholar]
- 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]
- Penman E., Lowry P. J., Wass J. A., Marks V., Dawson A. M., Besser G. M., Rees L. H. Molecular forms of somatostatin in normal subjects and in patients with pancreatic somatostatinoma. Clin Endocrinol (Oxf) 1980 Jun;12(6):611–620. doi: 10.1111/j.1365-2265.1980.tb01383.x. [DOI] [PubMed] [Google Scholar]
- Penman E., Wass J. A., Lund A., Lowry P. J., Stewart J., Dawson A. M., Besser G. M., Rees L. H. Development and validation of a specific radioimmunoassay for somatostatin in human plasma. Ann Clin Biochem. 1979 Jan;16(1):15–25. doi: 10.1177/000456327901600103. [DOI] [PubMed] [Google Scholar]
- Penman E., Wass J. A., Medbak S., Morgan L., Lewis J. M., Besser G. M., Rees L. H. Response of circulating immunoreactive somatostatin to nutritional stimuli in normal subjects. Gastroenterology. 1981 Oct;81(4):692–699. [PubMed] [Google Scholar]
- Polonsky K. S., Shoelson S. E., Docherty H. M. Plasma somatostatin 28 increases in response to feeding in man. J Clin Invest. 1983 May;71(5):1514–1518. doi: 10.1172/JCI110907. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rabbani S. N., Patel Y. C. Measurement and characterization of somatostatin-14-like immunoreactivity in human urine. J Clin Endocrinol Metab. 1988 May;66(5):1050–1055. doi: 10.1210/jcem-66-5-1050. [DOI] [PubMed] [Google Scholar]
- Reichlin S. Somatostatin (second of two parts). N Engl J Med. 1983 Dec 22;309(25):1556–1563. doi: 10.1056/NEJM198312223092506. [DOI] [PubMed] [Google Scholar]
- Reubi J. C., Rivier J., Perrin M., Brown M., Vale W. Specific high affinity binding sites for somatostatin-28 on pancreatic beta-cells: differences with brain somatostatin receptors. Endocrinology. 1982 Mar;110(3):1049–1051. doi: 10.1210/endo-110-3-1049. [DOI] [PubMed] [Google Scholar]
- Rouiller D., Schusdziarra V., Harris V., Unger R. H. Release of pancreatic and gastric somatostatin-like immunoreactivity in response to the octapeptide of cholecystokinin, secretin gastric inhibitory polypeptide, and gastrin-17 in dogs. Endocrinology. 1980 Aug;107(2):524–529. doi: 10.1210/endo-107-2-524. [DOI] [PubMed] [Google Scholar]
- Ruggere M. D., Patel Y. C. Hepatic metabolism of somatostatin-14 and somatostatin-28: immunochemical characterization of the metabolic fragments and comparison of cleavage sites. Endocrinology. 1985 Jul;117(1):88–96. doi: 10.1210/endo-117-1-88. [DOI] [PubMed] [Google Scholar]
- Ruggere M. D., Patel Y. C. Somatostatin metabolism by the isolated rat lung. Endocrinology. 1985 Nov;117(5):1870–1873. doi: 10.1210/endo-117-5-1870. [DOI] [PubMed] [Google Scholar]
- Sacks H. S., Terry L. C., Wright R. K., Stentz F. B. Somatostatin metabolism: differences in clearance of N-terminal and central portions of molecule during perfusion of rat liver. Am J Physiol. 1984 Mar;246(3 Pt 1):G226–G234. doi: 10.1152/ajpgi.1984.246.3.G226. [DOI] [PubMed] [Google Scholar]
- Samols E., Bonner-Weir S., Weir G. C. Intra-islet insulin-glucagon-somatostatin relationships. Clin Endocrinol Metab. 1986 Feb;15(1):33–58. doi: 10.1016/s0300-595x(86)80041-x. [DOI] [PubMed] [Google Scholar]
- Schusdziarra V., Zyznar E., Rouiller D., Boden G., Brown J. C., Arimura A., Unger R. H. Splanchnic somatostatin: a hormonal regulator of nutrient homeostasis. Science. 1980 Feb 1;207(4430):530–532. doi: 10.1126/science.7352262. [DOI] [PubMed] [Google Scholar]
- Schusdziarra V., Zyznar E., Rouiller D., Harris V., Unger R. H. Free somatostatin in the circulation: amounts and molecular sizes of somatostatin-like immunoreactivity in portal, aortic, and vena caval plasma of fasting and meal-stimulated dogs. Endocrinology. 1980 Nov;107(5):1572–1576. doi: 10.1210/endo-107-5-1572. [DOI] [PubMed] [Google Scholar]
- Seal A., Yamada T., Debas H., Hollinshead J., Osadchey B., Aponte G., Walsh J. Somatostatin-14 and -28: clearance and potency on gastric function in dogs. Am J Physiol. 1982 Aug;243(2):G97–102. doi: 10.1152/ajpgi.1982.243.2.G97. [DOI] [PubMed] [Google Scholar]
- Shoelson S. E., Polonsky K. S., Nakabayashi T., Jaspan J. B., Tager H. S. Circulating forms of somatostatinlike immunoreactivity in human plasma. Am J Physiol. 1986 Apr;250(4 Pt 1):E428–E434. doi: 10.1152/ajpendo.1986.250.4.E428. [DOI] [PubMed] [Google Scholar]
- 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]
- Taborsky G. J., Jr, Ensinck J. W. Contribution of the pancreas to circulating somatostatin-like immunoreactivity in the normal dog. J Clin Invest. 1984 Jan;73(1):216–223. doi: 10.1172/JCI111194. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tsuda K., Sakurai H., Seino Y., Seino S., Tanigawa K., Kuzuya H., Imura H. Somatostatin-like immunoreactivity in human peripheral plasma measured by radioimmunoassay following affinity chromatography. Diabetes. 1981 Jun;30(6):471–474. doi: 10.2337/diab.30.6.471. [DOI] [PubMed] [Google Scholar]
- Utsumi M., Makimura H., Ishihara K., Morita S., Baba S. Determination of immunoreactive somatostatin in rat plasma and responses to arginine, glucose and glucagon infusion. Diabetologia. 1979 Nov;17(5):319–323. doi: 10.1007/BF01235888. [DOI] [PubMed] [Google Scholar]
- Von Schenck H., Larsson I., Thorell J. I. Improved radioiodination of glucagon with the lactoperoxidase method. Influence of pH on iodine substitution. Clin Chim Acta. 1976 Jun 1;69(2):225–232. doi: 10.1016/0009-8981(76)90500-3. [DOI] [PubMed] [Google Scholar]
- Wass J. A., Penman E., Dryburgh J. R., Tsiolakis D., Goldberg P. L., Dawson A. M., Besser G. M., Rees L. H. Circulating somatostatin after food and glucose in man. Clin Endocrinol (Oxf) 1980 Jun;12(6):569–574. doi: 10.1111/j.1365-2265.1980.tb01377.x. [DOI] [PubMed] [Google Scholar]
- Zyznar E. S., Pietri A. O., Harris V., Unger R. H. Evidence for the hormonal status of somatostatin in man. Diabetes. 1981 Oct;30(10):883–886. doi: 10.2337/diab.30.10.883. [DOI] [PubMed] [Google Scholar]