Summary
The islets of Langerhans of diabetic and non-diabetic patients with different degrees of islet amyloidosis were studied by electron microscopy. The islet amyloid exhibited the typical fine fibrillar ultrastructure and was mainly located interstitially. Adjacent to the β cells the amyloid fibrils were often highly orientated perpendicularly to the cell surface and bundles of amyloid fibrils entered in deep plasmalemmal invaginations of the cells. This was more rarely seen in other types of cell. The epithelial cells exhibited no signs of increased activity. Macrophages were common in the amyloid masses. Amyloid occurred in invaginations of these cells but usually the fibrils showed no orientation. The capillaries, the fibrocytes and the mast cells were not so closely related to the amyloid. These findings probably indicate that the amyloid of the islets of Langerhans is a product of degenerating β cells even if other possibilities are not excluded.
Zusammenfassung
Die Ultrastruktur der Langerhansschen Inseln bei der Inselamyloidose.
Die Langerhansschen Inseln diabetischer und nicht-diabetischer Patienten mit verschiedenen Schweregraden einer Inselamyloidose wurden elektronenmikroskopisch untersucht. Das Inselamyloid zeigte eine typische feinfibrilläre Ultrastruktur und war vorwiegend interstitiell lokalisiert. In der Nachbarschaft der β-Zellen waren die Amyloidfibrillen oft senkrecht zur Zelloberfläche orientiert, wobei Bündel von Amyloidifibrillen in tiefe Invaginationen der Zellgrenzmembran hineinragten. Diese Beobachtung fand sich selten bei den anderen Inselzelltypen. Die Epithelzellen zeigten keine Hinweise auf eine gesteigerte Aktivität. Im Bereich der Amyloidmassen fanden sich in der Regel Makrophagen. Das Amyloid war in den Invaginationen dieser Zellen erkennbar, allerdings gewöhnlich nicht in paralleler Orientierung. Capillaren, Fibrocyten und Mastzellen waren dem Amyloid weniger dicht benachbart. Aus den Befunden wird der Schluß gezogen, daß das Amyloid der Langerhansschen Inseln ein Produkt degenerierender β-Zellen darstellt. Andere Möglichkeiten der Entstehung lassen sich allerdings nicht ausschließen.
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References
Ahronheim, J. H.: The nature of the hyaline material in the pancreatic islands in diabetes mellitus. Amer. J. Path. 19, 873–882 (1943).
Arey, J. B.: Nature of the hyaline changes in islands of Langerhans in diabetes mellitus. Arch. Path. 36, 32–38 (1943).
Beek, C. van: Amyloid-neerslag in de eilandjes van Langerhans bij diabetes mellitus. Ned. T. Geneesk. 83, 646–654 (1939).
Berns, A. W., Owens, C. T., Blumenthal, H. T.: A histo- and immunopathologic study of the vessels and islets of Langerhans of the pancreas in diabetes mellitus. J. Geront. 19, 179–189 (1964).
Björkman, N., Hellerström, C., Hellman, B., Petersson, B.: The cell types in the endocrine pancreas of the human fetus. Z. Zellforsch. 72, 425–445 (1966).
Caesar, R.: Die Feinstruktur von Milz und Leber bei experimenteller Amyloidose. Z. Zellforsch. 52, 653–673 (1960).
Cohen, A. S.: The constitution and genesis of amyloid. In: International review of experimental pathology (Richter, G. W. and Epstein, M. A., eds.), vol. 4, p. 159. New York: Academic Press 1965.
Cohen, A. S.: Preliminary chemical analysis of partially purified amyloid fibrils. Lab. Invest. 15, 66–83 (1966).
Cohen, A. S.: High resolution ultrastructure, immunology and biochemistry of amyloid. In: Amyloidosis (Mandema, E., Ruinen, L., Scholten, J. H., and Cohen, A. S., eds.), p. 149. Amsterdam: Excerpta Medica Foundation 1968.
Cohen, A. S., Calkins, E.: Electron microscopic observations on a fibrous component in amyloid of diverse origins. Nature (Lond.) 183, 1202–1203 (1959).
Cohen, A. S., Gross, E., Shirahama, T.: The light and electron microscopic autoradiographic demonstration of local amyloid formation in spleen explants. Amer. J. Path. 47, 1079–1112 (1965).
De Petris, S., Karlsbad, G., Pernis, B.: Filamentous structures in the cytoplasm of normal mononuclear phagocytes. J. Ultrastruct. Res. 7, 39–55 (1962).
Dumont, A.: Ultrastructural study of the maturation of peritoneal macrophages in the hamster. J. Ultrastruct. Res. 29, 191–209 (1969).
Ehrlich, J. C., Ratner, I. M.: Amyloidosis of the islets of Langerhans. A restudy of islet hyalin in diabetic and nondiabetic individuals. Amer. J. Path. 38, 49–59 (1961).
Gellerstedt, N.: Die elektive, insuläre (Para-) Amyloidose der Bauchspeicheldrüse. Zugleich ein Beitrag zur Kenntnis der „senilen Amyloidose“. Beitr. path. Anat. 101, 1–13 (1938).
Grimelius, L.: An electron microscopic study of silver stained adult human pancreatic islet cells, with reference to a new silver nitrate procedure. Acta Soc. Med. upsalien. 74, 28–48 (1969).
Gueft, B., Ghidoni, J. J.: The site of formation and ultrastructure of amyloid. Amer. J. Path. 43, 837–854 (1963).
Gueft, B., Kikkawa, Y., Hirschl, S.: An electron-microscopic study of amyloidosis from different species. In: Amyloidosis (Mandema, E., Ruinen, L., Scholten, J. H., and Cohen, A. S., eds.), p. 172. Amsterdam: Excerpta Medica Foundation 1968.
Hartroft, W. S.: The islets of Langerhans in man visualized by phase contrast microscopy. Proc. Amer. Diab. Ass. 10, 46–61 (1950).
Kawanishi, H., Akazawa, Y., Machii, B.: Islets of Langerhans in normal and diabetic humans. Ultrastructure and histochemistry, with special reference to hyalinosis. Acta path. jap. 16, 177–197 (1966).
Kikkawa, Y., Suzuki, K., Gueft, B.: Amino acid composition of urea-extracted amyloid. In: Amyloidosis (Mandema, E., Ruinen, L., Scholten, J. H., and Cohen, A. S., eds.), p. 293. Amsterdam: Excerpta Medica Foundation 1968.
Kohama, M., Moriwaki, K., Abe, H.: Electron microscopic observations of pancreatic beta cells of diabetic patients. Folia endocr. jap. 44, 1107–1109 (1969).
Lacy, P. E.: Pancreatic beta cell. In: Aetiology of diabetes mellitus and its complications. Ciba Foundation Colloquia on Endocrinology, vol. 15, p. 75. Boston: Little, Brown & Company 1964.
Lacy, P. E.: Functional morphology of the islet cells. In: Nobel Symposium 13. Pathogenesis of Diabetes Mellitus (Cerasi, E., and Luft, R., eds.), p. 109. Stockholm: Almqvist & Wiksell 1970.
Luft, J. H.: Improvements in epoxy resin embedding methods. J. biophys. biochem. Cytol. 9, 409–414 (1961).
Mallory, F. B.: The principles of pathologic histology. Philadelphia and London: W. B. Saunders Co. 1925.
Mowry, R. W., Scott, J. E.: Observations on the basophilia of amyloids. Histochemie 10, 8–32 (1967).
Pearse, A. G. E.: Histochemistry. Theoretical and applied, 2nd ed. London: J. & A. Churchill Ltd. 1960.
Pearse, A. G. E., Ewen, S. W. B., Polak, J. M.: The genesis of apudamyloid in endocrine polypeptide tumours: histochemical distinction from immunamyloid. Virchows Arch. Abt. B 10, 93–107 (1972).
Ranløv, P., Wanstrup, J.: Ultrastructural investigations on the cellular morphogenesis of experimental mouse amyloidosis. Acta path. microbiol. scand. 71, 575–591 (1967).
Ranløv, P., Wanstrup, J.: Electron-microscopic demonstration of intracellular amyloid in experimental mouse amyloidosis. In: Amyloidosis (Mandema, E., Ruinen, L., Scholten, J. H., and Cohen, A. S., eds.), p. 74. Amsterdam: Excerpta Medica Foundation 1968.
Reynolds, E. S.: The use of lead citrate at high pH as an electron-opaque stain in electron microscopy. J. Cell Biol. 17, 208–212 (1963).
Schwartz, P.: Über Amyloidose des Gehirns, der Langerhansschen Inseln und des Herzens alter Personen. Zbl. allg. Path. path. Anat. 108, 169–187 (1965).
Shirahama, T., Cohen, A. S.: A Congo red staining method for epoxy-embedded amyloid. J. Histochem. Cytochem. 14, 725–729 (1966).
Shirahama, T., Cohen, A. S.: Fine structure of the glomerulus in human and experimental renal amyloidosis. Amer. J. Path. 51, 869–911 (1967).
Shirahama, T., Cohen, A. S.: Lysosomal breakdown of amyloid fibrils by macrophages. Amer. J. Path. 63, 463–485 (1971).
Shirahama, T., Cohen, A. S., Rodgers, O. G.: Phagocytosis of amyloid: In vitro interaction of mouse peritoneal macrophages with human amyloid fibrils and their accelerated uptake after dye binding. Exp. molec. Path. 14, 110–123 (1971).
Sorenson, G. D., Bari, W. A.: Murine amyloid deposits and cellular relationships. In: Amyloidosis (Mandema, E., Ruinen, L., Scholten, J. H., and Cohen, A. S., eds.), p. 58. Amsterdam: Excerpta Medica Foundation 1968.
Sorenson, G. D., Heefner, W. A., Kirkpatrick, J. B.: Experimental amyloidosis. II. Light and electron microscopic observations of liver. Amer. J. Path. 44, 629–644 (1964).
Teilum, G.: Pathogenesis of amyloidosis. The two-phase cellular theory of local secretion Acta path. microbiol. scand. 61, 21–45 (1964).
Watson, M. L.: Staining of tissue sections for electron microscopy with heavy metals. J. biophys., biochem. Cytol. 4, 475–478 (1958).
Westermark, P.: Mast cells in the islets of Langerhans in insular amyloidosis. Virchows Arch. Abt. A 354, 17–23 (1971).
Westermark, P.: Quantitative studies of amyloid in the islets of Langerhans. Upsala J. Med. Sci. 77, 91–94 (1972a).
Westermark, P.: Ultrastructure of capillaries and interstitial cells in human pancreatic islets. Upsala J. Med. Sci., in press, 1972b.
Westermark, P., Grimelius, L.: The pancreatic islet cells in insular amyloidosis in human diabetic and non-diabetic adults. In preparation, 1972.
Yamada, Y.: Pathologic study on amyloidosis. Amyloidosis of the islets of Langerhans in diabetes mellitus. Bull. Yamaguchi med. Sch. 15, 227–250 (1968).
Zucker-Franklin, D., Franklin, E. C.: Intracellular localization of human amyloid by fluorescence and electron microscopy. Amer. J. Path. 59, 23–41 (1970).
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Supported by the Swedish Medical Research Council (project No. B73-12X-102-09B, the Research Fund of the Swedish Diabetes Association, the Swedish Society for Medical Research and the Medical Faculty of Uppsala. Thanks are due to Ann-Charlotte Hallner, Lena Rönning and Anders Strand for their skilled technical assistance.
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Westermark, P. Fine structure of islets of Langerhans in insular amyloidosis. Virchows Arch. Abt. A Path. Anat. 359, 1–18 (1973). https://doi.org/10.1007/BF00549079
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DOI: https://doi.org/10.1007/BF00549079