Skip to main content

Intracellular Formation of Amyloid Fibrils in B-Cells of Human Insulinoma and Pre-Diabetic Monkey Islets

  • Chapter

Abstract

Amyloid formed from islet amyloid polypeptide (lAPP) is present in pancreatic islets of spontaneously diabetic humans, monkeys and cats and in some insulinomas. The factors which cause amyloid deposition are unknown but may be related to abnormal processing or catabolism of the peptide. To determine the sites at which fibrils are formed, immunoreactivity for lAPP (lAPP-IR) was examined electron microscopically in 16 specimens of insulinoma and in pancreatic autopsy specimens from two pre-diabetic monkeys. In 9/16 insulinomas, lAPP-IR was detected on extracellular amyloid and in 6 of these, IAPP-IR was located on intracellular fibrils some of which were membrane bound. IAPP-IR was found on the radially arranged islet amyloid of pre-diabetic monkey islets. IAPP-IR on fibrils at intracellular sites suggests that amyloidosis may commence inside the cell. Subsequently, the fibrils would be extruded from the cell or become extracellular as a result of cell death.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Clark, A., Wells, C.A, Buley, I.D., et al. (1988) ‘Islet amyloid, Increased A-cells, reduced B-cells&exocrine fibrosis: quantitative changes in the pancreas in type 2 diabetes’, Diabetes Res. 9, 151–159.

    PubMed  CAS  Google Scholar 

  2. Bell, E.T. (1952) ‘Hyalinization in the islets of Langerhans in diabetes mellitus’, Diabetes 1, 341–344.

    PubMed  CAS  Google Scholar 

  3. Yano, B.L, Hayden, D.W., and Johnson. K.H. (1981) ‘Feline insular amyloid association with diabetes mellitus’, Vet Pathol. 18, 621–627.

    PubMed  CAS  Google Scholar 

  4. Howard, C.F. (1986) ‘Longitudinal studies on the development of diabetes in individual Macaca nigra’, Diabetologia 29, 301–306.

    Article  PubMed  Google Scholar 

  5. Westermark, P., Wemstedt, C., Wilander, E. et al. (1987) ‘Amyloid fibrils in human insulinoma&islets of Langerhans of the diabetic cat are derived from a neuropeptide-like protein also present in normal cells’, Proc. Natl. Acad. Sci USA 84, 3881–3885.

    Article  PubMed  CAS  Google Scholar 

  6. Cooper, G.J.S., Willis, A.C., Clark, A., et al. (1987) ‘Purification&characterization of a peptide from amyloid-rich pancreas of type 2 diabetic patients’, Proc Natl Acad Sci USA 84, 8628–8632.

    Article  PubMed  CAS  Google Scholar 

  7. Clark, A., Edwards, C.A., Ostle, L.R., et al. (1989) ‘Localisation of islet amyloid peptide in lipofuscin bodies and secretory granules of human B-cells and in islets of Type II diabetic subjects’, Cell Tiss Res. 257, 179–185.

    CAS  Google Scholar 

  8. Lukinius, A., Wilander, E., Westermark, G.T., et al. (1989) ‘Co-localisation of islet amyloid polypeptide and insulin in the B-cell secretory granules of human pancreatic islets’, Diabetologia 32, 240–244.

    Article  PubMed  CAS  Google Scholar 

  9. Westermark. P., Grimelius, L., Polak, J.M., et al. (1977) ‘Amyloid in polypeptide hormone producing tumours’, Lab Invest. 37. 212–215.

    PubMed  CAS  Google Scholar 

  10. Betsholtz. C., Christmanson, L, Engstrom, U., et al. (1990) ‘Structure of cat islet amyloid polypeptide&identification of amino acid residues of potential significance for islet amyloid formation’, Diabetes 39, 118–122.

    Article  PubMed  CAS  Google Scholar 

  11. Hansen, B.C. and Bodkin, N.L (1986) ‘Heterogeneity of insulin responses: phases leading to type 2 (non-insulin-dependent) diabetes mellitus in the rhesus monkey’, Diabetologia 29, 713–719.

    Article  PubMed  CAS  Google Scholar 

  12. Sanke, T., Bell, G.I., Semple. C., et al. (1990) ‘An islet amyloid peptide is derived from an 89-amino-acid precursor by proteolytic processing’, J Biol. Chem. 263, 17243–17246.

    Google Scholar 

  13. Westermark, P., Engstrom, U., Westermark. G.T., et al. (1989) ‘Islet amyloid polypeptide (lAPP)&pro-IAPP immunoreactivity in human islets of Langerhans’, Diabetes Res. Clin Prac. 7, 219–226.

    Article  CAS  Google Scholar 

  14. Ward. W.K., LaCava. E.C., Paquette. T.L. et al. (1987) ‘Disproportionate elevation of immunoreactive proinsulin in Type 2 (non-insulin dependent) diabetes mellitus&in experimental insulin resistance’, Diabetologia 30, 698–702.

    Article  PubMed  CAS  Google Scholar 

  15. Turner, R.C. and Heding, LG. (1977) ‘Plasma proinsulin, C-peptide&insulin in diagnostic suppression tests for insulinomas’, Diabetologia 13, 571–577.

    Article  PubMed  CAS  Google Scholar 

  16. Kanatsuka, A., Makino, H., Ohsawa, H., et al. (1989) ‘Secretion of islet amyloid polypeptide in response to glucose’, FEBS Lett 259, 199–201.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1991 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Clark, A. et al. (1991). Intracellular Formation of Amyloid Fibrils in B-Cells of Human Insulinoma and Pre-Diabetic Monkey Islets. In: Natvig, J.B., et al. Amyloid and Amyloidosis 1990. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-3284-8_113

Download citation

  • DOI: https://doi.org/10.1007/978-94-011-3284-8_113

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-5450-8

  • Online ISBN: 978-94-011-3284-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics