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. 1987 Jun;84(11):3881–3885. doi: 10.1073/pnas.84.11.3881

Amyloid fibrils in human insulinoma and islets of Langerhans of the diabetic cat are derived from a neuropeptide-like protein also present in normal islet cells.

P Westermark, C Wernstedt, E Wilander, D W Hayden, T D O'Brien, K H Johnson
PMCID: PMC304980  PMID: 3035556

Abstract

Amyloid deposits localized to the islets of Langerhans are typical of non-insulin-dependent human diabetes mellitus and of diabetes mellitus in adult cats. Amyloid deposits also commonly occur in insulin-producing pancreatic tumors. We have purified a major protein--insulinoma or islet amyloid polypeptide (IAPP)--from human and cat islet amyloid and from amyloid of a human insulinoma. IAPP from human insulinoma contained 37 amino acid residues and had a theoretical molecular mass of 3850 Da. The amino acid sequence is unique but has greater than 40% identity with the human calcitonin gene-related peptide. A partial amino acid sequence of cat islet IAPP corresponding to positions 1-27 of human insulinoma IAPP was identical to the human IAPP except for substitutions in three positions. An antiserum raised to a synthetic human insulinoma IAPP-(7-17) undecapeptide showed specific immunohistochemical reactivity with human and cat islet amyloid and with islet B cells. The significance of this pancreatic neuropeptide-like protein is unknown, but it is suggested that it may exert an important endocrine regulatory effect.

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Selected References

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

  1. Amara S. G., Jonas V., Rosenfeld M. G., Ong E. S., Evans R. M. Alternative RNA processing in calcitonin gene expression generates mRNAs encoding different polypeptide products. Nature. 1982 Jul 15;298(5871):240–244. doi: 10.1038/298240a0. [DOI] [PubMed] [Google Scholar]
  2. Benditt E. P., Eriksen N., Hermodson M. A., Ericsson L. H. The major proteins of human and monkey amyloid substance: Common properties including unusual N-terminal amino acid sequences. FEBS Lett. 1971 Dec 1;19(2):169–173. doi: 10.1016/0014-5793(71)80506-9. [DOI] [PubMed] [Google Scholar]
  3. Blobel G., Dobberstein B. Transfer of proteins across membranes. I. Presence of proteolytically processed and unprocessed nascent immunoglobulin light chains on membrane-bound ribosomes of murine myeloma. J Cell Biol. 1975 Dec;67(3):835–851. doi: 10.1083/jcb.67.3.835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cohen D. H., Feiner H., Jensson O., Frangione B. Amyloid fibril in hereditary cerebral hemorrhage with amyloidosis (HCHWA) is related to the gastroentero-pancreatic neuroendocrine protein, gamma trace. J Exp Med. 1983 Aug 1;158(2):623–628. doi: 10.1084/jem.158.2.623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Costa P. P., Figueira A. S., Bravo F. R. Amyloid fibril protein related to prealbumin in familial amyloidotic polyneuropathy. Proc Natl Acad Sci U S A. 1978 Sep;75(9):4499–4503. doi: 10.1073/pnas.75.9.4499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Eanes E. D., Glenner G. G. X-ray diffraction studies on amyloid filaments. J Histochem Cytochem. 1968 Nov;16(11):673–677. doi: 10.1177/16.11.673. [DOI] [PubMed] [Google Scholar]
  7. Fisher L. A., Kikkawa D. O., Rivier J. E., Amara S. G., Evans R. M., Rosenfeld M. G., Vale W. W., Brown M. R. Stimulation of noradrenergic sympathetic outflow by calcitonin gene-related peptide. Nature. 1983 Oct 6;305(5934):534–536. doi: 10.1038/305534a0. [DOI] [PubMed] [Google Scholar]
  8. GEPTS W. Die histopathologischen Veränderungen der Langerhansschen Inseln und ihre Bedeutung in der Frage der Pathogenese des menschlichen Diabetes. Endokrinologie. 1958 Jul;36(3-4):185–211. [PubMed] [Google Scholar]
  9. Gejyo F., Yamada T., Odani S., Nakagawa Y., Arakawa M., Kunitomo T., Kataoka H., Suzuki M., Hirasawa Y., Shirahama T. A new form of amyloid protein associated with chronic hemodialysis was identified as beta 2-microglobulin. Biochem Biophys Res Commun. 1985 Jun 28;129(3):701–706. doi: 10.1016/0006-291x(85)91948-5. [DOI] [PubMed] [Google Scholar]
  10. Glenner G. G. Amyloid deposits and amyloidosis. The beta-fibrilloses (first of two parts). N Engl J Med. 1980 Jun 5;302(23):1283–1292. doi: 10.1056/NEJM198006053022305. [DOI] [PubMed] [Google Scholar]
  11. Glenner G. G., Terry W., Harada M., Isersky C., Page D. Amyloid fibril proteins: proof of homology with immunoglobulin light chains by sequence analyses. Science. 1971 Jun 11;172(3988):1150–1151. doi: 10.1126/science.172.3988.1150. [DOI] [PubMed] [Google Scholar]
  12. Glenner G. G., Wong C. W. Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun. 1984 May 16;120(3):885–890. doi: 10.1016/s0006-291x(84)80190-4. [DOI] [PubMed] [Google Scholar]
  13. Johnson K. H., Hayden D. W., O'Brien T. D., Westermark P. Spontaneous diabetes mellitus-islet amyloid complex in adult cats. Am J Pathol. 1986 Nov;125(2):416–419. [PMC free article] [PubMed] [Google Scholar]
  14. Johnson K. H., Westermark P., Nilsson G., Sletten K., O'Brien T. D., Hayden D. W. Feline insular amyloid: immunohistochemical and immunochemical evidence that the amyloid is insulin-related. Vet Pathol. 1985 Sep;22(5):463–468. doi: 10.1177/030098588502200505. [DOI] [PubMed] [Google Scholar]
  15. Ludwig G., Heitner H. Zur Häufigkeit der Inselamyloidose des Pankreas beim Diabetes mellitus. Z Gesamte Inn Med. 1967 Dec 15;22(24):814–819. [PubMed] [Google Scholar]
  16. Lundqvist M., Wilander E. A simple procedure for immunocytochemical- and silver-staining of endocrine cells in the same section. Acta Pathol Microbiol Immunol Scand A. 1983 Nov;91(6):493–494. doi: 10.1111/j.1699-0463.1983.tb02785.x. [DOI] [PubMed] [Google Scholar]
  17. MACLEAN N., OGILVIE R. F. Quantitative estimation of the pancreatic islet tissue in diabetic subjects. Diabetes. 1955 Sep-Oct;4(5):367–376. doi: 10.2337/diab.4.5.367. [DOI] [PubMed] [Google Scholar]
  18. O'Brien T. D., Johnson K. H., Hayden D. W. Pancreatic ganglioneuronal amyloid. Occurrence in diabetic cats with islet amyloidosis. Am J Pathol. 1985 Jun;119(3):430–435. [PMC free article] [PubMed] [Google Scholar]
  19. Pearse A. G., Ewen S. W., Polak J. M. The genesis of apudamyloid in endocrine polypeptide tumours: histochemical distinction from immunamyloid. Virchows Arch B Cell Pathol. 1972;10(2):93–107. doi: 10.1007/BF02899719. [DOI] [PubMed] [Google Scholar]
  20. Rosenfeld M. G., Mermod J. J., Amara S. G., Swanson L. W., Sawchenko P. E., Rivier J., Vale W. W., Evans R. M. Production of a novel neuropeptide encoded by the calcitonin gene via tissue-specific RNA processing. Nature. 1983 Jul 14;304(5922):129–135. doi: 10.1038/304129a0. [DOI] [PubMed] [Google Scholar]
  21. Sletten K., Westermark P., Natvig J. B. Characterization of amyloid fibril proteins from medullary carcinoma of the thyroid. J Exp Med. 1976 Apr 1;143(4):993–998. doi: 10.1084/jem.143.4.993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Steenbergh P. H., Höppener J. W., Zandberg J., Lips C. J., Jansz H. S. A second human calcitonin/CGRP gene. FEBS Lett. 1985 Apr 22;183(2):403–407. doi: 10.1016/0014-5793(85)80820-6. [DOI] [PubMed] [Google Scholar]
  23. Sternini C., Brecha N. Immunocytochemical identification of islet cells and nerve fibers containing calcitonin gene-related peptide-like immunoreactivity in the rat pancreas. Gastroenterology. 1986 May;90(5 Pt 1):1155–1163. doi: 10.1016/0016-5085(86)90380-x. [DOI] [PubMed] [Google Scholar]
  24. Westermark P., Grimelius L., Polak J. M., Larsson L. I., Van Noorden S., Wilander E., Pearse A. G. Amyloid in polypeptide hormone-producing tumors. Lab Invest. 1977 Aug;37(2):212–215. [PubMed] [Google Scholar]
  25. Westermark P., Wernstedt C., Wilander E., Sletten K. A novel peptide in the calcitonin gene related peptide family as an amyloid fibril protein in the endocrine pancreas. Biochem Biophys Res Commun. 1986 Nov 14;140(3):827–831. doi: 10.1016/0006-291x(86)90708-4. [DOI] [PubMed] [Google Scholar]
  26. Westermark P., Wilander E. The influence of amyloid deposits on the islet volume in maturity onset diabetes mellitus. Diabetologia. 1978 Nov;15(5):417–421. doi: 10.1007/BF01219652. [DOI] [PubMed] [Google Scholar]
  27. Yano B. L., Hayden D. W., Johnson K. H. Feline insular amyloid: association with diabetes mellitus. Vet Pathol. 1981 Sep;18(5):621–627. doi: 10.1177/030098588101800507. [DOI] [PubMed] [Google Scholar]
  28. Yano B. L., Hayden D. W., Johnson K. H. Feline insular amyloid: incidence in adult cats with no clinicopathologic evidence of overt diabetes mellitus. Vet Pathol. 1981 May;18(3):310–315. doi: 10.1177/030098588101800303. [DOI] [PubMed] [Google Scholar]

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