Advertisement

Virchows Archiv B

, 47:313 | Cite as

Intermediate cells in the adult human pancreas

Contribution to the transformation of differentiated cells in vertebrates
  • L. Cossel
Article

Summary

Problems associated with the transformation of differentiated cells in vertebrate organisms are discussed based on electron microscopical results of intermediate cells (i.e. cells with morphological characteristics of exocrine acinar cells and endocrine cells of Langerhans’ islets) in the pancreas of human adults with chronic insulin-dependent diabetes mellitus. In this context, reference is made to experimental results of Scarpelli, Rao, and coworkers relating to the occurrence of hepatocyte-like cells in the pancreas of Syrian golden hamsters (Rao and Scarpelli 1980; Scarpelli and Rao 1981; Rao et al. 1983). These observations show that exocrine acinar cells of the pancreas may, even beyond the neonatal period, become transformed, depending upon different triggering stimuli, into different endocrine islet cells, or into hepatocytes, this being accomplished either directly or by new formation of cells (regeneration) with abnormal differentiation (metaplasia). Obviously, transformation is effected through a change in the activation of gene loci: the normally stably blocked genes are partially or completely deblocked for the functions of different endocrine islets cells or hepatocytes, and the original genetic expression of exocrine pancreatic functions is blocked either partially or completely.

The results presented and quoted in this paper suggest that in all differentiated cells derived from the endoderm of the foregut, such as duct cells, exocrine and endocrine pancreatic cells, and hepatocytes, functional programs are retained which can be modified in the manner quoted to enable partial or complete transformation into one or another of these differentiated cells in the adult organism.

Key words

Cell differentiation Cellular transformation Pancreatic intermediate cells Hepatocytelike cells in the pancreas 

References

  1. Becker K, Wendel U, Przyrembel H, Tsotsalas M, Müntefering H, Bremer HJ (1978) Beta cell nesidioblastosis. Eur J Pediatr 127:75–89PubMedCrossRefGoogle Scholar
  2. Björkman N, Hellman B (1964) Ultrastructure of the islets of Langerhans in the duck. Acta Anat 56:348–367Google Scholar
  3. Brown RE, Still WJS (1970) Acinar-islet cells in the exocrine pancreas of the adult cat. Am J Dig Dis 15:327–335PubMedCrossRefGoogle Scholar
  4. Cossel L, Schade J, Verlohren HJ, Lohmann D, Mättig H (1983) Ultrastructural, immunohistological, and clinical findings in the pancreas in insulin-dependent diabetes mellitus (IDDM) of long duration. Zbl Allg Pathol 128:147–159Google Scholar
  5. Cossel L, Binh T, Verlohren HJ, Lohmann D, Mättig H (1984) Elektronenmikroskopische Befunde an den A Zellen der Langerhansschen Inseln beim Diabetes mellitus (IDDM, NIDDM). Zbl Allg Pathol 129:323–341Google Scholar
  6. Dieterlen-Lièvre F (1965) Étude morphologique et expérimentale de la différenciation du pancréas chez l’embryon de poulet. Bull Biol 99:1–116Google Scholar
  7. Falkmer S, Östberg I (1977) Comparative morphology of pancreatic islets in animals. In: Volk BW, Wellmann KF (eds) The diabetic pancreas. Bailliére Tidall, London, pp 15–59Google Scholar
  8. Faller A (1966) Elektronenmikroskopische Untersuchungen von azinoinsulinären Übergängen im Pankreas normaler und alloxandiabetischer Ratten. Verh Anat Ges 61:113–124PubMedGoogle Scholar
  9. Faller A (1969) Elektronenmikroskopische Differenzen verschiedener Inselzelltypen im Pankreas normaler Albinoratten. Z Zellforsch Mikrosk Anat 97:226–248PubMedCrossRefGoogle Scholar
  10. Forsmann A (1976) The ultrastructure of the cell types in the endocrine pancreas of the horse. Cell Tiss Res 167:179–195CrossRefGoogle Scholar
  11. Gould VE, Memoli VA, Dardi LE, Gould NS (1981) Nesidiodysplasia and nesidioblastosis of infancy. Alterations with and without associated hyperinsulinaemic hypoglycaemia. Scand J Gastroenterol 16 [Suppl] 70:129–142Google Scholar
  12. Gould VE, Memoli VA, Dardi LE, Gould NS (1983) Nesidiodysplasia and nesidioblastosis of infancy: Structural and functional correlations with the syndrome of hyperinsulinemic hypoglycemia. Ped Pathol 1:7–13CrossRefGoogle Scholar
  13. Gusek W, Kracht J (1959) Elektronenmikroskopische Untersuchungen über Inselwachstum und acino-insuläre Transformation. Frankfurter Z Pathol 70:98–106Google Scholar
  14. Hellerström C (1977) Growth pattern of pancreatic islets in animals. In: Volk BW, Wellmann KF (eds) The diabetic pancreas. Baillière Tindall, London, pp 61–97Google Scholar
  15. Herman L, Sato T, Fitzgerald PJ (1963) Electron microscopy of “acinar-islet” cells in the rat pancreas. Fed Proc Am Soc Exp Biol 22:603Google Scholar
  16. Herman L, Sato T, Fitzgerald PJ (1964) The pancreas. In: Kurtz SM (ed) Electron microscopy anatomy. Academic Press, New York, London, pp 59–95Google Scholar
  17. House EL, Nace PF, Tassoni JP (1956) Alloxan diabetes in the hamster: organ changes during the first day. Endocrinology 59:433–443PubMedGoogle Scholar
  18. House EL (1958) A histological study of the pancreas, liver and kidney both during and after recovery from alloxan diabetes. Endocrinology 62:189–200PubMedCrossRefGoogle Scholar
  19. Hughes H (1947) Cyclical changes in the islets of Langerhans in the rat pancreas. J Anat 81:82–92PubMedGoogle Scholar
  20. Jaffe R, Hashida Y, Yunis EJ (1980) Pancreatic pathology in hyperinsulinemic hypoglycemia of infancy. Lab Invest 42:356–365PubMedGoogle Scholar
  21. Johnson DD (1950) Alloxan administration in the guinea-pig. A study of the regenerating phase in the islands of Langerhans. Endocrinology 47:393–398PubMedGoogle Scholar
  22. Klöppel G (1981) Endokrines Pankreas und Diabetes mellitus. In: Doerr W, Seifert G (eds) Pathologie der endokrinen Organe. Vol 14/I. Springer, Berlin Heidelberg New York, pp 523–728Google Scholar
  23. Kobayashi K (1966) Electron microscope studies of the Langerhans islets in the toad pancreas. Arch Histol Jpn 26:439–482PubMedGoogle Scholar
  24. Laguesse ME (1905) Ilots endocrines et formes de transition dans le lobule pancréatique (homme). Cr Séance Soc Biol 58:542–544Google Scholar
  25. Leduc EH, Jones EE (1968) Acinar-islet cell transformation in mouse pancreas. J Ultrastruct Res 24:165–169PubMedCrossRefGoogle Scholar
  26. Like AA, Orci L (1972) Embryogenesis of the human pancreatic islets: a light and electron microscopic study. Diabetes 21 [Suppl] 2:511–534Google Scholar
  27. Logothetopoulos J (1972) In: Handbook of physiology, Sect 7, Vol 1, Steiner DF, Freinkel N (eds) American Physiological Society, Washington DC, pp 67Google Scholar
  28. Mättig H, Lohmann D, Verlohren H J, Cossel L, Schade J, Schneider E (1983) Eine schonende Methode zur Gewinnung von Pankreasgewebe für spezielle morphologische und biochem- ische Untersuchungen. Deutsche Z Verdau Stoffwechselkr 43:65–71Google Scholar
  29. Mankowski A (1902) Über die makroskopischen Veränderungen des Pankreas nach Unterbin- dung einzelner Theile und über einige mikrochemische Besonderheiten der Langerhansschen Inseln. Arch Mikrosk Anat Entwicklungsmech 59:286–294Google Scholar
  30. Melmed RN, Benitez CJ, Holt SJ (1972) Intermediate cells of the pancreas I. Ultrastructural characterization. J Cell Sci 11:449–475PubMedGoogle Scholar
  31. Melmed RN, Turner RC, Holt SJ (1973) Intermediate cells of the pancreas. II. The effects of dietary soybean trypsin inhibitor on acinar-β cell structure and function in the rat. J Cell Sci 13:279–295PubMedGoogle Scholar
  32. Melmed RN, Benitez CJ, Holt SJ (1973) Intermediate cells of the pancreas. III Selective autophagy and destruction of β-granules in intermediate cells of the pancreas induced by alloxan and streptozotocin. J Cell Sci 13:297–315PubMedGoogle Scholar
  33. Melmed RN (1979) Intermediate cells of the pancreas, an appraisal. Gastroenterology 76: 196–201PubMedGoogle Scholar
  34. Mihail N, Cracium C (1982) An ultrastructural description of the cell type in the endocrine pancreas of the pigeon. Anat Anz 152:229–237PubMedGoogle Scholar
  35. Mikami S, Mutoh K (1971) Light- and electron microscopic studies of the pancreatic islet cells in the chicken under normal and experimental conditions. Z Zellforsch Mikrosk Anat 116:205–227PubMedCrossRefGoogle Scholar
  36. Orci L, Rufener C, Pictet R, Renold AE, Rouiller C (1970) The structure and metabolism of the pancreatic islets. Falkmer S, Hellman B, Täljedal IB (eds) Pergamon Press, Oxford, pp 37Google Scholar
  37. Patent GJ, Alfert M (1967) Histological changes in the pancreatic islets of alloxan-treated mice, with comments on β-cell regeneration. Acta Anat 66:504–519PubMedGoogle Scholar
  38. Pearse AGE, Polak JM, Heath CM (1973) Development, differentiation and derivation of the endocrine polypeptide cells of the mouse pancreas (Immunofluorescence, cytochemical and ultrastructural studies). Diabetologia 9:120–129PubMedCrossRefGoogle Scholar
  39. Pictet R, Gonet A (1966) Cellules mixtes (exocrines et endocrines) dans le pancréas de la souris à piquants Acomys cahirinus. Cr Séance Soc Biol 262:1123–1125Google Scholar
  40. Pictet R, Orci L, Gonet AE, Rouiller C, Renold AE (1967) Ultrastructural studies of the hyperplastic islets of Langerhans of spiny mice (Acomys cahirinus) before and during development of hyperglycaemia. Diabetologia 3:188–211PubMedCrossRefGoogle Scholar
  41. Rao MS, Scarpelli DG (1980) Transdifferentiation of pancreatic acinar cells to hepatocytes in the Syrian golden hamster. J Cell Biol 87:26 aGoogle Scholar
  42. Rao MS, Subbarao V, Luetteke N, Scarpelli DG (1983) Further characterization of carcinogen-induced hepatocytelike cells in hamster pancreas. AJP 110:89–94PubMedGoogle Scholar
  43. Reynolds ES (1963) The use of lead citrate at high pH as an electronopaque stain in electron microscopy. J Cell Biol 17:208–212PubMedCrossRefGoogle Scholar
  44. Rhoten WB (1970) The cell population in pancreatic islets of Amphisbaenidae — A light- and electron microscopic study. Anat Rec 167:401–422PubMedCrossRefGoogle Scholar
  45. Scarpelli DG, Rao MS (1981) Differentiation of regenerating pancreatic cells into hepatocyte-like cells. Proc Natl Acad Sci [USA] 78:2577–2581CrossRefGoogle Scholar
  46. Shino A, Iwatsuka H (1970) Morphological observations on pancreatic islets of spontaneous diabetic mice “Yellow KK”. Endocrinol Jpn 17:459–476PubMedGoogle Scholar
  47. Shorr SS, Bloom FE (1970) Acino-insular cells in normal rat pancreas. Yale J Biol Med 43:47–49PubMedGoogle Scholar
  48. Sternberger LA, Handy PH, Cuculis JJ, Meyer HC (1970) An unlabelled antibody method of immunocytochemistry. J Histochem Cytochem 18:315–340PubMedGoogle Scholar
  49. Stoeckenius W, Kracht J (1958) Elektronenmikroskopische Untersuchungen an den Langer- hansschen Inseln der Ratte. Endokrinologie 36:135–142PubMedGoogle Scholar
  50. Woerner CA (1938) Studies of the islands of Langerhans after continuous intravenous injection of dextrose. Anat Rec 71:33–49CrossRefGoogle Scholar
  51. Zagury D, de Brux J, Ancla M, Leger L (1961) Étude des ilots de Langerhans du pancréas humain au microscope électronique. Presse Med 69:887–890PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1984

Authors and Affiliations

  • L. Cossel
    • 1
  1. 1.Institute of PathologyKarl-Marx-UniversityLeipzigGDR

Personalised recommendations