Skip to main content
SpringerLink
Log in

Intermediate cells in the adult human pancreas

Contribution to the transformation of differentiated cells in vertebrates

  • Published:
Virchows Archiv B

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.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Becker K, Wendel U, Przyrembel H, Tsotsalas M, Müntefering H, Bremer HJ (1978) Beta cell nesidioblastosis. Eur J Pediatr 127:75–89

    Article  PubMed  CAS  Google Scholar 

  • Björkman N, Hellman B (1964) Ultrastructure of the islets of Langerhans in the duck. Acta Anat 56:348–367

    Google Scholar 

  • Brown RE, Still WJS (1970) Acinar-islet cells in the exocrine pancreas of the adult cat. Am J Dig Dis 15:327–335

    Article  PubMed  CAS  Google Scholar 

  • 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 128:147–159

    CAS  Google Scholar 

  • 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 129:323–341

    CAS  Google Scholar 

  • Dieterlen-Lièvre F (1965) Étude morphologique et expérimentale de la différenciation du pancréas chez l’embryon de poulet. Bull Biol 99:1–116

    Google Scholar 

  • 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 15–59

    Google Scholar 

  • Faller A (1966) Elektronenmikroskopische Untersuchungen von azinoinsulinären Übergängen im Pankreas normaler und alloxandiabetischer Ratten. Verh Anat Ges 61:113–124

    PubMed  CAS  Google Scholar 

  • Faller A (1969) Elektronenmikroskopische Differenzen verschiedener Inselzelltypen im Pankreas normaler Albinoratten. Z Zellforsch Mikrosk Anat 97:226–248

    Article  PubMed  CAS  Google Scholar 

  • Forsmann A (1976) The ultrastructure of the cell types in the endocrine pancreas of the horse. Cell Tiss Res 167:179–195

    Article  Google Scholar 

  • 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] 70:129–142

    CAS  Google Scholar 

  • 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 1:7–13

    Article  CAS  Google Scholar 

  • Gusek W, Kracht J (1959) Elektronenmikroskopische Untersuchungen über Inselwachstum und acino-insuläre Transformation. Frankfurter Z Pathol 70:98–106

    Google Scholar 

  • Hellerström C (1977) Growth pattern of pancreatic islets in animals. In: Volk BW, Wellmann KF (eds) The diabetic pancreas. Baillière Tindall, London, pp 61–97

    Google Scholar 

  • Herman L, Sato T, Fitzgerald PJ (1963) Electron microscopy of “acinar-islet” cells in the rat pancreas. Fed Proc Am Soc Exp Biol 22:603

    Google Scholar 

  • Herman L, Sato T, Fitzgerald PJ (1964) The pancreas. In: Kurtz SM (ed) Electron microscopy anatomy. Academic Press, New York, London, pp 59–95

    Google Scholar 

  • House EL, Nace PF, Tassoni JP (1956) Alloxan diabetes in the hamster: organ changes during the first day. Endocrinology 59:433–443

    PubMed  CAS  Google Scholar 

  • House EL (1958) A histological study of the pancreas, liver and kidney both during and after recovery from alloxan diabetes. Endocrinology 62:189–200

    Article  PubMed  CAS  Google Scholar 

  • Hughes H (1947) Cyclical changes in the islets of Langerhans in the rat pancreas. J Anat 81:82–92

    PubMed  CAS  Google Scholar 

  • Jaffe R, Hashida Y, Yunis EJ (1980) Pancreatic pathology in hyperinsulinemic hypoglycemia of infancy. Lab Invest 42:356–365

    PubMed  CAS  Google Scholar 

  • Johnson DD (1950) Alloxan administration in the guinea-pig. A study of the regenerating phase in the islands of Langerhans. Endocrinology 47:393–398

    PubMed  CAS  Google Scholar 

  • 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 523–728

    Google Scholar 

  • Kobayashi K (1966) Electron microscope studies of the Langerhans islets in the toad pancreas. Arch Histol Jpn 26:439–482

    PubMed  CAS  Google Scholar 

  • Laguesse ME (1905) Ilots endocrines et formes de transition dans le lobule pancréatique (homme). Cr Séance Soc Biol 58:542–544

    Google Scholar 

  • Leduc EH, Jones EE (1968) Acinar-islet cell transformation in mouse pancreas. J Ultrastruct Res 24:165–169

    Article  PubMed  CAS  Google Scholar 

  • Like AA, Orci L (1972) Embryogenesis of the human pancreatic islets: a light and electron microscopic study. Diabetes 21 [Suppl] 2:511–534

    Google Scholar 

  • Logothetopoulos J (1972) In: Handbook of physiology, Sect 7, Vol 1, Steiner DF, Freinkel N (eds) American Physiological Society, Washington DC, pp 67

    Google Scholar 

  • 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 43:65–71

    Google Scholar 

  • 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 59:286–294

    Google Scholar 

  • Melmed RN, Benitez CJ, Holt SJ (1972) Intermediate cells of the pancreas I. Ultrastructural characterization. J Cell Sci 11:449–475

    PubMed  CAS  Google Scholar 

  • 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 13:279–295

    PubMed  CAS  Google Scholar 

  • 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 13:297–315

    PubMed  CAS  Google Scholar 

  • Melmed RN (1979) Intermediate cells of the pancreas, an appraisal. Gastroenterology 76: 196–201

    PubMed  CAS  Google Scholar 

  • Mihail N, Cracium C (1982) An ultrastructural description of the cell type in the endocrine pancreas of the pigeon. Anat Anz 152:229–237

    PubMed  CAS  Google Scholar 

  • 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 116:205–227

    Article  PubMed  CAS  Google Scholar 

  • 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 37

    Google Scholar 

  • Patent GJ, Alfert M (1967) Histological changes in the pancreatic islets of alloxan-treated mice, with comments on β-cell regeneration. Acta Anat 66:504–519

    PubMed  CAS  Google Scholar 

  • 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 9:120–129

    Article  PubMed  CAS  Google Scholar 

  • Pictet R, Gonet A (1966) Cellules mixtes (exocrines et endocrines) dans le pancréas de la souris à piquants Acomys cahirinus. Cr Séance Soc Biol 262:1123–1125

    Google Scholar 

  • 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 3:188–211

    Article  PubMed  CAS  Google Scholar 

  • Rao MS, Scarpelli DG (1980) Transdifferentiation of pancreatic acinar cells to hepatocytes in the Syrian golden hamster. J Cell Biol 87:26 a

    Google Scholar 

  • Rao MS, Subbarao V, Luetteke N, Scarpelli DG (1983) Further characterization of carcinogen-induced hepatocytelike cells in hamster pancreas. AJP 110:89–94

    PubMed  CAS  Google Scholar 

  • Reynolds ES (1963) The use of lead citrate at high pH as an electronopaque stain in electron microscopy. J Cell Biol 17:208–212

    Article  PubMed  CAS  Google Scholar 

  • Rhoten WB (1970) The cell population in pancreatic islets of Amphisbaenidae — A light- and electron microscopic study. Anat Rec 167:401–422

    Article  PubMed  CAS  Google Scholar 

  • Scarpelli DG, Rao MS (1981) Differentiation of regenerating pancreatic cells into hepatocyte-like cells. Proc Natl Acad Sci [USA] 78:2577–2581

    Article  CAS  Google Scholar 

  • Shino A, Iwatsuka H (1970) Morphological observations on pancreatic islets of spontaneous diabetic mice “Yellow KK”. Endocrinol Jpn 17:459–476

    PubMed  CAS  Google Scholar 

  • Shorr SS, Bloom FE (1970) Acino-insular cells in normal rat pancreas. Yale J Biol Med 43:47–49

    PubMed  CAS  Google Scholar 

  • Sternberger LA, Handy PH, Cuculis JJ, Meyer HC (1970) An unlabelled antibody method of immunocytochemistry. J Histochem Cytochem 18:315–340

    PubMed  CAS  Google Scholar 

  • Stoeckenius W, Kracht J (1958) Elektronenmikroskopische Untersuchungen an den Langer- hansschen Inseln der Ratte. Endokrinologie 36:135–142

    PubMed  CAS  Google Scholar 

  • Woerner CA (1938) Studies of the islands of Langerhans after continuous intravenous injection of dextrose. Anat Rec 71:33–49

    Article  CAS  Google Scholar 

  • Zagury D, de Brux J, Ancla M, Leger L (1961) Étude des ilots de Langerhans du pancréas humain au microscope électronique. Presse Med 69:887–890

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Pathology, Karl-Marx-University, Liebigstraße 26, 7010, Leipzig, GDR

    L. Cossel

Authors
  1. L. Cossel
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cossel, L. Intermediate cells in the adult human pancreas. Virchows Archiv B Cell Pathol 47, 313–328 (1984). https://doi.org/10.1007/BF02890214

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02890214

Key words

Search

Navigation