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. 1969 Aug;48(8):1453–1460. doi: 10.1172/JCI106111

The gastrointestinal stimulus to insulin release

I. Secretin

D J Chisholm 1, J D Young 1, L Lazarus 1
PMCID: PMC322372  PMID: 5796357

Abstract

The gastrointestinal stimulus to the release of insulin has been investigated in man by the use of a radioimmunoassay for secretin. Serum secretin levels rose rapidly after the oral ingestion of glucose or protein and preceded the elevation of serum insulin. An intravenous infusion of highly purified secretin caused a release of insulin when the serum secretin levels were within the physiological range.

Infusion of hydrochloric acid into the duodenum caused an elevation of serum secretin and serum insulin levels in normal subjects. A similar response of secretin and insulin was seen after intravenous infusion of pentagastrin even when the acid stimulus to the duodenum was prevented. The latter observation suggests that pentagastrin (and probably gastrin) releases secretin by a direct humoral effect which is later fortified by the arrival of gastric acid in the duodenum.

These studies suggest that secretin participates in the augmentation of insulin release after oral stimuli, and that a rapid sequence of humoral events takes place, gastrin releasing secretin and secretin releasing insulin. Subsequently secretin release would be augmented by a local stimulus in the duodenum and insulin release by the rising level of blood glucose or amino acids.

This humoral system, which could also involve other gastrointestinal hormones, would provide a mechanism for facilitating the release of insulin to coincide with the onset of metabolite absorption.

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Selected References

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

  1. Bassett J. M., Wallace A. L. Diluents for insulin standards in immunoassay of insulin in undiluted ovine plasma by a double antibody technique. J Endocrinol. 1966 Sep;36(1):99–100. doi: 10.1677/joe.0.0360099. [DOI] [PubMed] [Google Scholar]
  2. Boyns D. R., Jarrett R. J., Keen H. Intestinal hormones and plasma insulin: an insulinotropic action of secretin. Br Med J. 1967 Jun 10;2(5553):676–678. doi: 10.1136/bmj.2.5553.676. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Caridis D. T., Porter J. F., Smith G. Detection of histamine in venous blood from the stomach during acid secretion evoked by intravenous pentagastrin. Lancet. 1968 Jun 15;1(7555):1281–1282. doi: 10.1016/s0140-6736(68)92294-0. [DOI] [PubMed] [Google Scholar]
  4. Cerasi E., Luft R. "What is inherited--what is added" hypothesis for the pathogenesis of diabetes mellitus. Diabetes. 1967 Sep;16(9):615–627. doi: 10.2337/diab.16.9.615. [DOI] [PubMed] [Google Scholar]
  5. DUPRE J. AN INTESTINAL HORMONE AFFECTING GLUCOSE DISPOSAL IN MAN. Lancet. 1964 Sep 26;2(7361):672–673. doi: 10.1016/s0140-6736(64)92481-x. [DOI] [PubMed] [Google Scholar]
  6. Deckert T. Stimulation of insulin secretion by glucagon and secretin. Acta Endocrinol (Copenh) 1968 Apr;57(4):578–584. doi: 10.1530/acta.0.0570578. [DOI] [PubMed] [Google Scholar]
  7. Dupré J., Curtis J. D., Waddell R. W., Beck J. C. Alimentary factors in the endocrine response to administration of arginine in man. Lancet. 1968 Jul 6;2(7558):28–29. doi: 10.1016/s0140-6736(68)92895-x. [DOI] [PubMed] [Google Scholar]
  8. Dupré J., Rojas L., White J. J., Unger R. H., Beck J. C. Effects of secretin on insulin and glucagon in portal and peripheral blood in man. Lancet. 1966 Jul 2;2(7453):26–27. doi: 10.1016/s0140-6736(66)91750-8. [DOI] [PubMed] [Google Scholar]
  9. ELRICK H., STIMMLER L., HLAD C. J., Jr, ARAI Y. PLASMA INSULIN RESPONSE TO ORAL AND INTRAVENOUS GLUCOSE ADMINISTRATION. J Clin Endocrinol Metab. 1964 Oct;24:1076–1082. doi: 10.1210/jcem-24-10-1076. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. GOODFRIEND T. L., LEVINE L., FASMAN G. D. ANTIBODIES TO BRADYKININ AND ANGIOTENSIN: A USE OF CARBODIIMIDES IN IMMUNOLOGY. Science. 1964 Jun 12;144(3624):1344–1346. doi: 10.1126/science.144.3624.1344. [DOI] [PubMed] [Google Scholar]
  12. GREENWOOD F. C., HUNTER W. M., GLOVER J. S. THE PREPARATION OF I-131-LABELLED HUMAN GROWTH HORMONE OF HIGH SPECIFIC RADIOACTIVITY. Biochem J. 1963 Oct;89:114–123. doi: 10.1042/bj0890114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. IZZO J. L., RONCONE A., IZZO M. J., BALE W. F. RELATIONSHIP BETWEEN DEGREE OF IODINATION OF INSULIN AND ITS BIOLOGICAL, ELECTROPHORETIC, AND IMMUNOCHEMICAL PROPERTIES. J Biol Chem. 1964 Nov;239:3749–3754. [PubMed] [Google Scholar]
  14. Jorpes E., Mutt V. Sekretin och glukagon som regulatorer för insulininsöndringen till blodet. Nord Med. 1967 Mar 9;77(10):301–304. [PubMed] [Google Scholar]
  15. Lazarus L., Young J. D. Radioimmunoassay of human growth hormone using ion exchange resin. J Clin Endocrinol Metab. 1966 Feb;26(2):213–218. doi: 10.1210/jcem-26-2-213. [DOI] [PubMed] [Google Scholar]
  16. Mahler R. J., Weisberg H. Failure of endogenous stimulation of secretin and pancreozymin release to influence serum-insulin. Lancet. 1968 Mar 2;1(7540):448–451. doi: 10.1016/s0140-6736(68)92780-3. [DOI] [PubMed] [Google Scholar]
  17. McIntyre N., Holdsworth C. D., Turner D. S. Intestinal factors in the control of insulin secretion. J Clin Endocrinol Metab. 1965 Oct;25(10):1317–1324. doi: 10.1210/jcem-25-10-1317. [DOI] [PubMed] [Google Scholar]
  18. Meade R. C., Kneubuhler H. A., Schulte W. J., Barboriak J. J. Stimulation of insulin secretion by pancreozymin. Diabetes. 1967 Mar;16(3):141–144. doi: 10.2337/diab.16.3.141. [DOI] [PubMed] [Google Scholar]
  19. Moore B. On the treatment of Diabetus mellitus by acid extract of Duodenal Mucous Membrane. Biochem J. 1906;1(1):28–38. doi: 10.1042/bj0010028. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Perley M. J., Kipnis D. M. Plasma insulin responses to oral and intravenous glucose: studies in normal and diabetic sujbjects. J Clin Invest. 1967 Dec;46(12):1954–1962. doi: 10.1172/JCI105685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pfeiffer E. F., Telib M., Ammon J., Melani F., Ditschuneit H. Direkte Stimulierung der Insulin-Sekretion in vitro durch Sekretin. Dtsch Med Wochenschr. 1965 Sep 17;90(38):1663–1669. doi: 10.1055/s-0028-1113397. [DOI] [PubMed] [Google Scholar]
  22. Rubenstein A. H., Cho S., Steiner D. F. Evidence for proinsulin in human urine and serum. Lancet. 1968 Jun 22;1(7556):1353–1355. doi: 10.1016/s0140-6736(68)92040-0. [DOI] [PubMed] [Google Scholar]
  23. SAMOLS E., MARRI G., MARKS V. PROMOTION OF INSULIN SECRETION BY GLUCAGON. Lancet. 1965 Aug 28;2(7409):415–416. doi: 10.1016/s0140-6736(65)90761-0. [DOI] [PubMed] [Google Scholar]
  24. SUNDBERG A., GRONBERG A. Diabetes mellitus and pernicious anaemia. Acta Med Scand. 1960 Feb 17;166:147–150. doi: 10.1111/j.0954-6820.1960.tb17365.x. [DOI] [PubMed] [Google Scholar]
  25. Steele R. The influences of insulin on the hepatic metabolism of glucose. Ergeb Physiol. 1966;57:91–189. [PubMed] [Google Scholar]
  26. Thayer W. R., Jr, Martin H. F. Histidine decarboxylase inhibition and gastric secretion. Am J Dig Dis. 1967 Oct;12(10):1050–1061. doi: 10.1007/BF02233265. [DOI] [PubMed] [Google Scholar]
  27. Unger R. H., Ketterer H., Dupré J., Eisentraut A. M. The effects of secretin, pancreozymin, and gastrin on insulin and glucagon secretion in anesthetized dogs. J Clin Invest. 1967 Apr;46(4):630–645. doi: 10.1172/JCI105565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Unger R. H., Ketterer H., Eisentraut A., Dupré J. Effect of secretin on insulin secretion. Lancet. 1966 Jul 2;2(7453):24–26. doi: 10.1016/s0140-6736(66)91749-1. [DOI] [PubMed] [Google Scholar]
  29. Young J. D., Kraegen E. W. Simultaneous assay of insulin and glucagon in serum. Aust J Exp Biol Med Sci. 1968 Dec;46(6):697–705. doi: 10.1038/icb.1968.176. [DOI] [PubMed] [Google Scholar]
  30. Young J. D., Lazarus L., Chisholm D. J., Atkinson F. F. Radioimmunoassay of secretin in human serum. J Nucl Med. 1968 Dec;9(12):641–642. [PubMed] [Google Scholar]

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