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. 1987;28(Suppl):51–55. doi: 10.1136/gut.28.suppl.51

Do insulin and the insulin like growth factors (IGFs) stimulate growth of the exocrine pancreas?

J Mössner 1, C D Logsdon 1, I D Goldfine 1, J A Williams 1
PMCID: PMC1434571  PMID: 2446963

Abstract

Previous in vivo studies have suggested a long term regulatory role for insulin in the exocrine pancreas. Furthermore, we reported that pancreatic acini have specific receptors for IGF I and II, and using different techniques (acid washing, trypsinisation, electron microscope autoradiography), that CCK8 reduces the internalisation of IGF II. To now directly study the long term role for IGF and insulin in the exocrine pancreas we used AR42J cells, a rat cell line that is derived from a transplantable tumour of the acinar pancreas. Hormone binding studies with 125I-labelled hormones indicated that those cells have insulin receptors, relatively fewer receptors for IGF II but in contrast with normal acini no detectable IGF I receptors. Insulin at concentrations as low as 1 nm stimulated the growth of AR42J cells, as measured by an increase in cell number, DNA and protein content. At 100 nM insulin had maximal effects stimulating the growth by about 50%. IGF I and II had only very weak growth promoting effects probably due to their interaction with the insulin receptor. Additionally insulin increased amylase synthesis over the same concentration range that it stimulated growth. But immunoprecipitation studies revealed that insulin induced a selective increase of amylase synthesis over general protein synthesis. These studies indicate, therefore, that insulin is a growth promoting hormone for AR42J cells and that additionally it seems to specifically regulate amylase synthesis. The role for the IGFs in the exocrine pancreas, however, still remains to be determined.

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Selected References

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

  1. Adams S. O., Nissley S. P., Kasuga M., Foley T. P., Jr, Rechler M. M. Receptors for insulin-like growth factors and growth effects of multiplication-stimulating activity (rat insulin-like growth factor II) in rat embryo fibroblasts. Endocrinology. 1983 Mar;112(3):971–978. doi: 10.1210/endo-112-3-971. [DOI] [PubMed] [Google Scholar]
  2. Adler G., Kern H. F. Regulation of exocrine pancreatic secretory process by insulin in vivo. Horm Metab Res. 1975 Jul;7(4):290–296. doi: 10.1055/s-0028-1093717. [DOI] [PubMed] [Google Scholar]
  3. BENABDELJLIL A., PALLA J. C., DESNUELLE P. EFFECT OF INSULIN ON PANCREATIC AMYLASE AND CHYMOTRYPSINOGEN. Biochem Biophys Res Commun. 1965 Jan 4;18:71–75. doi: 10.1016/0006-291x(65)90884-3. [DOI] [PubMed] [Google Scholar]
  4. CHEY W. Y., SHAY H., SHUMAN C. R. EXTERNAL PANCREATIC SECRETION IN DIABETES MELLITUS. Ann Intern Med. 1963 Dec;59:812–821. doi: 10.7326/0003-4819-59-6-812. [DOI] [PubMed] [Google Scholar]
  5. Christophe J., Camus J., Deschodt-Lanckman M., Rathe J., Robberecht P., Vandermeers-Piret M. C., Vandermeers A. Factors regulating biosynthesis, intracellular transport and secretion of amylase and lipase in the rat exocrine pancreas. Horm Metab Res. 1971 Nov;3(6):393–403. doi: 10.1055/s-0028-1094128. [DOI] [PubMed] [Google Scholar]
  6. Domschke W., Tympner F., Domschke S., Demling L. Exocrine pancreatic function in juvenile diabetics. Am J Dig Dis. 1975 Apr;20(4):309–312. doi: 10.1007/BF01237787. [DOI] [PubMed] [Google Scholar]
  7. Frier B. M., Faber O. K., Binder C., Elliot H. L. The effect of residual insulin secretion on exocrine pancreatic function in juvenile-onset diabetes mellitus. Diabetologia. 1978 May;14(5):301–304. doi: 10.1007/BF01223020. [DOI] [PubMed] [Google Scholar]
  8. Frier B. M., Saunders J. H., Wormsley K. G., Bouchier I. A. Exocrine pancreatic function in juvenile-onset diabetes mellitus. Gut. 1976 Sep;17(9):685–691. doi: 10.1136/gut.17.9.685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Goldfine I. D., Smith G. J. Binding of insulin to isolated nuclei. Proc Natl Acad Sci U S A. 1976 May;73(5):1427–1431. doi: 10.1073/pnas.73.5.1427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gospodarowicz D., Moran J. S. Stimulation of division of sparse and confluent 3T3 cell populations by a fibroblast growth factor, dexamethasone, and insulin. Proc Natl Acad Sci U S A. 1974 Nov;71(11):4584–4588. doi: 10.1073/pnas.71.11.4584. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Korc M., Sankaran H., Wong K. Y., Williams J. A., Goldfine I. D. Insulin receptors in isolated mouse pancreatic acini. Biochem Biophys Res Commun. 1978 Sep 29;84(2):293–299. doi: 10.1016/0006-291x(78)90169-9. [DOI] [PubMed] [Google Scholar]
  12. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  13. Massagué J., Czech M. P. The subunit structures of two distinct receptors for insulin-like growth factors I and II and their relationship to the insulin receptor. J Biol Chem. 1982 May 10;257(9):5038–5045. [PubMed] [Google Scholar]
  14. Megyesi K., Kahn C. R., Roth J., Froesch E. R., Humbel R. E., Zapf J., Neville D. M., Jr Insulin and non-suppressible insulin-like activity (NSILA-s): evidence for separate plasma membrane receptor sites. Biochem Biophys Res Commun. 1974 Mar 15;57(1):307–315. doi: 10.1016/s0006-291x(74)80391-8. [DOI] [PubMed] [Google Scholar]
  15. Mossner J., Roach E., Goldfine I. D., Williams J. A. Autoradiographic analysis of 125I-insulin-like growth factor II internalization into pancreatic acini. Diabetes Res Clin Pract. 1986 May;2(2):75–82. doi: 10.1016/s0168-8227(86)80063-8. [DOI] [PubMed] [Google Scholar]
  16. Mössner J., Logsdon C. D., Potau N., Williams J. A., Goldfine I. D. Effect of intracellular Ca2+ on insulin-like growth factor II. internalization into pancreatic acini. Roles of insulin and cholecystokinin. J Biol Chem. 1984 Oct 25;259(20):12350–12356. [PubMed] [Google Scholar]
  17. Mössner J., Logsdon C. D., Williams J. A., Goldfine I. D. Insulin, via its own receptor, regulates growth and amylase synthesis in pancreatic acinar AR42J cells. Diabetes. 1985 Sep;34(9):891–897. doi: 10.2337/diab.34.9.891. [DOI] [PubMed] [Google Scholar]
  18. Otsuki M., Williams J. A. Direct modulation of pancreatic CCK receptors and enzyme secretion by insulin in isolated pancreatic acini from diabetic rats. Diabetes. 1983 Mar;32(3):241–246. doi: 10.2337/diab.32.3.241. [DOI] [PubMed] [Google Scholar]
  19. Otsuki M., Williams J. A. Effect of diabetes mellitus on the regulation of enzyme secretion by isolated rat pancreatic acini. J Clin Invest. 1982 Jul;70(1):148–156. doi: 10.1172/JCI110588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Rechler M. M., Podskalny J. M., Goldfine I. D., Wells C. A. DNA synthesis in human fibroblasts: stimulation by insulin and by nonsuppressible insulin-like activity (NSILA-S). J Clin Endocrinol Metab. 1974 Sep;39(3):512–521. doi: 10.1210/jcem-39-3-512. [DOI] [PubMed] [Google Scholar]
  21. Smith G. L., Temin H. M. Purified multiplication-stimulating activity from rat liver cell conditioned medium: comparison of biological activities with calf serum, insulin, and somatomedin. J Cell Physiol. 1974 Oct;84(2):181–192. doi: 10.1002/jcp.1040840204. [DOI] [PubMed] [Google Scholar]
  22. Söling H. D., Unger K. O. The role of insulin in the regulation of -amylase synthesis in the rat pancreas. Eur J Clin Invest. 1972 Jun;2(4):199–212. doi: 10.1111/j.1365-2362.1972.tb00645.x. [DOI] [PubMed] [Google Scholar]
  23. VACCA J. B., HENKE W. J., KNIGHT W. A., Jr THE EXOCRINE PANCREAS IN DIABETES MELLITUS. Ann Intern Med. 1964 Aug;61:242–247. doi: 10.7326/0003-4819-61-2-242. [DOI] [PubMed] [Google Scholar]
  24. Williams J. A., Bailey A. C., Preissler M., Goldfine I. D. Insulin regulation of sugar transport in isolated pancreatic acini from diabetic mice. Diabetes. 1982 Aug;31(8 Pt 1):674–682. doi: 10.2337/diab.31.8.674. [DOI] [PubMed] [Google Scholar]
  25. Zapf J., Rinderknecht E., Humbel R. E., Froesch E. R. Nonsuppressible insulin-like activity (NSILA) from human serum: recent accomplishments and their physiologic implications. Metabolism. 1978 Dec;27(12):1803–1828. doi: 10.1016/0026-0495(78)90267-6. [DOI] [PubMed] [Google Scholar]

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