Disturbed Growth of the Endocrine Pancreas

  • S. Falkmer
  • U. Askensten


In the large neuroendocrine system, the islets of Langerhans belong to the third component [18], namely the classical endocrine glands of the human body. This endocrine parenchyma, like that of other neuroendocrine glands in the vertebrates, can be the subject of growth disturbances [25; 28]. Although a genuine aplasia of the islets of Langerhans has only exceptionally been reported in man [28], both hypoplastic/hyperplastic and genuinely neoplastic islet lesions do occur and form the underlying causes of several well-known clinical syndromes. The best examples of such diseases are (a) the hypoplastic condition diabetes mellitus; (b) the hyperplastic lesions in persistent neonatal hypoglycemia with hyperinsulinism and nesidioblastosis (PNHHN), and (c) the benign and malignant islet-cell neoplasms, where the hormone overproduction gives rise to a multitude of clinical syndromes [27]. Our review will focus on the hyperplastic disturbances of growth in endocrine pancreas, notably the pathogenesis and structural lesions in PNHHN. Here, we can offer some new observations on the ploidy of the hyperplastic insulin cells, as well as an account of some recent findings on the normal pre- and postnatal differentiation and maturation of the mammalian islet parenchyma.


Islet Cell Endocrine Pancreas Islet Hormone Insulin Cell Hyperinsulinemic Hypoglycemia 
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  1. 1.
    Andrew A (1984) The development of the gastro-entero-pancreatic neuroendocrine system in birds. In: Falkmer S, Håkanson R, Sundler F (eds) Evolution and tumour pathology of the neuroendocrine system. Elsevier, Amsterdam, pp 91–110Google Scholar
  2. 2.
    Auer GU, Askensten UG, Zetterberg A (1987) Microspectrophotometric nuclear DNA analysis in clinical tumour material. Adv Clin Cytol (to be published)Google Scholar
  3. 3.
    Bishop AE, Polak JM, Chesa PG, Timson CM, Bryant MG, Bloom SR (1981) Decrease of pancreatic somatostatin in neonatal nesidioblastosis. Diabetes 30:122–126PubMedCrossRefGoogle Scholar
  4. 4.
    Bondeson L, Ljungberg O (1984) Occult papillary thyroid carcinoma in the young and the aged. Cancer 53:1790–1792PubMedCrossRefGoogle Scholar
  5. 5.
    Bonner-Weir S, Like AA (1980) A dual population of islets of Langerhans in bovine pancreas. Cell Tissue Res 206:157–170PubMedCrossRefGoogle Scholar
  6. 6.
    Conlon JM, Dafgård E, Falkmer S, Thim L (1987) The primary structure of ratfish insulin reveals an unusual mode of proinsulin processing. FEBS Lett 208: 445–450CrossRefGoogle Scholar
  7. 7.
    Chejfec G, Falkmer S, Grimelius L, Jacobsson B, Rodensjö M, Wiedenmann B, Franke WW, Lee I, Gould VE (1987) Synaptophysin: a new marker for pancreatic neuroendocrine tumors. Am J Surg Pathol 11: 241–247PubMedCrossRefGoogle Scholar
  8. 8.
    Dahms BB, Landing BH, Blaskovics M, Roe TF (1980) Nesidioblastosis and other islet cell abnormalities in hyperinsulinemic hypoglycemia of childhood. Hum Pathol 11: 641–649PubMedCrossRefGoogle Scholar
  9. 9.
    Edström C (1973) Course of alloxan diabetes in duct-ligated rats. A functional and morphological study. Acta Path Microbiol Scand 81 A: 21–36Google Scholar
  10. 10.
    El-Salhy M, Falkmer S, Kramer KJ, Speirs RD (1983) Immunohistochemical investigations of neuropeptides in the brain, corpora cardiaca, and corpora allata of an adult lepidopteran insect, Manduca sexta (L). Cell Tissue Res 232: 295–317PubMedCrossRefGoogle Scholar
  11. 11.
    Falkmer S (1985) Comparative morphology of pancreatic islets in animals. In: Volk BW, Arquilla ER (eds) The diabetic pancreas, 2nd edn. Plenum, New York, pp 17–52Google Scholar
  12. 12.
    Falkmer S (1985) Phylogenetical aspects of the brain-gut axis, with special reference to islet hormones in invertebrates and lower vertebrates. In: Kobayashi H, Bern HA, Akihisa U (eds) Neurosecretion and the biology of neuropeptides. Jpn Sci Soc Press, Tokyo, pp 317–325Google Scholar
  13. 13.
    Falkmer S, Boquist L (1976) Onto- and phylogenetical aspects on insulin-producing islet cell tumors. Horm Metab Res 6 [Suppl]: 55–62PubMedGoogle Scholar
  14. 14.
    Falkmer S, Emdin SO (1981) Insulin evolution. In: Dodson G, Glusker JP, Sayre D (eds) Structural studies of molecules of biological interest. Oxford University Press, Oxford, pp 420–440Google Scholar
  15. 15.
    Falkmer S, Van Noorden S (1983) Ontogeny and phylogeny of the glucagon cell. Handb Exp Pharmacol 66/1:81–119CrossRefGoogle Scholar
  16. 16.
    Falkmer S, Søvik O, Vidnes J (1981 a) Immunohistochemical, morphometric, and clinical studies of the pancreatic islets in infants with persistent neonatal hypoglycemia of familial type with hyperinsulinism and nesidioblastosis. Acta Biol Med Germ 40: 39–54PubMedGoogle Scholar
  17. 17.
    Falkmer S, Rahier J, Søvik O, Vidnes J (1981 b) Significance of argyrophil parenchymal cells in the pancreatic islets in persistent neonatal hypoglycemia with hyperinsulinism of familial type. Ups J Med Sci 86:111–117PubMedCrossRefGoogle Scholar
  18. 18.
    Falkmer S, El-Salhy M, Titibach M (1984) Evolution of the neuroendocrine system in vertebrates. A review with particular reference to the phylogeny and postnatal maturation of the islet parenchyma. In: Falkmer S, Håkanson R, Sundler F (eds) Evolution and tumour pathology of the neuroendocrine system. Elsevier, Amsterdam, pp 59–87Google Scholar
  19. 19.
    Falkmer S, Gustafsson MKS, Sundler F (1985) Phylogenetic aspects of the neuroendocrine system. A minireview with particular reference to cells storing neurohormonal peptides in some primitive protostomian invertebrates (flatworms, annelids). Nord Psykiatr Tidsskr 39 [Suppl 11]: 21–30CrossRefGoogle Scholar
  20. 20.
    Falkmer S, Conlon JM, Dafgård E, Thim L (1986) Phylogenetic aspects on regulatory peptides, in particular islet hormones in some lower vertebrates. Exp Brain Res 16:195–200Google Scholar
  21. 21.
    Franssila KO, Harach HR (1986) Occult papillary carcinoma of the thyroid in children and young adults. A systemic autopsy study in Finland. Cancer 58: 715–719PubMedCrossRefGoogle Scholar
  22. 22.
    Gabbay KH, Gang DL (1978) Hypoglycemia in a three-months-old girl. N Engl J Med 299: 241–248CrossRefGoogle Scholar
  23. 23.
    Gould VE, Memoli VA, Dardi LE, Gould NS (1983) Nesidiodysplasia and nesidioblastosis of infancy: structural and functional correlations with the syndrome of hyperinsulinemic hypoglycemia. Pediatr Pathol 1: 7–31PubMedCrossRefGoogle Scholar
  24. 24.
    Havu N (1986) Enterochromaffin-like (ECL) cell carcinoids of gastric mucosa in rats after lifelong inhibition of gastric secretion. Digestion 35 [Suppl 1]: 42–56PubMedCrossRefGoogle Scholar
  25. 25.
    Heitz PU, Klöppel G (1984) Pancreatic endocrine tumours. In: Falkmer S, Håkanson R, Sundler F (eds) Evolution and tumour pathology of the neuroendocrine system. Elsevier, Amsterdam, pp 481–496Google Scholar
  26. 26.
    Jaffe R, Hashida Y, Yunis EJ (1980) Pancreatic pathology in hyperinsulinemic hypoglycemia of infancy. Lab Invest 42: 356–365PubMedGoogle Scholar
  27. 27.
    Klöppel G, Heitz PU (1984) Nesidioblastosis: A clinical entity with heterogenous lesions of the pancreas. In: Falkmer S, Håkanson R, Sundler F (eds) Evolution and tumour pathology of the neuroendocrine system. Elsevier, Amsterdam, pp 340–379Google Scholar
  28. 28.
    Klöppel G, Heitz PU (eds) (1984) Pancreatic pathology. Edinburgh, Livingstone, pp 1–240Google Scholar
  29. 29.
    Klöppel G, Willemer S, Stamm B, Häcki WH, Heitz PU (1986) Pancreatic lesions and hormonal profile of pancreatic tumors in multiple endocrine neoplasia type I. An immunocytochemical study of nine patients. Cancer 57:1824–1832PubMedCrossRefGoogle Scholar
  30. 30.
    Koufos A, Hansen MF, Copeland NG, Jenkins HA, Lampkin BC, Cavenee K (1985) Loss of heterozygosity in three embryonal tumours suggests a common pathogenetic mechanism. Nature 316: 330–334PubMedCrossRefGoogle Scholar
  31. 31.
    Kramer JL, Bell MJ, De Schryver K, Bower RJ, Ternberg JL, White NH (1982) Clinical and histologic indications for extensive pancreatic resection in nesidioblastosis. Am J Surg 143: 116–119PubMedCrossRefGoogle Scholar
  32. 32.
    Larsson L-I, Goltermann NR, de Magistris L, Rehfeld JF, Schwartz TW (1979) Somatostatin cell processes as pathways for paracrine secretion. Science 205:1393–1394PubMedCrossRefGoogle Scholar
  33. 33.
    McQuarrie I (1954) Idiopathic spontaneously occurring hypoglycemia in infants. Clinical significance of problem and treatment. Am J Dis Child 87: 399–428Google Scholar
  34. 34.
    Moazam F, Rodgers BM, Talbert JL, Rosenbloom AL (1982) Near-total pancreatectomy in persistent infantile hypoglycemia. Arch Surg 117:1151–1154PubMedGoogle Scholar
  35. 35.
    de Morais CF, Lopes EA, Bisi H, Alves VAF, de Marcede Santos RT (1986) Nesidioblastosis associated with congenital malformations of the heart. Morphological and immunohistochemical study of 5 necropsy cases. Pathol Res Pract 181:175–179PubMedCrossRefGoogle Scholar
  36. 36.
    Newman GR, Jasani B, Williams ED (1986) Multiple hormone storage by polycrine cells in the pancreas (from a case of nesidioblastosis). Histochem J 18: 67–79PubMedCrossRefGoogle Scholar
  37. 37.
    O’Neill GS, Falkmer S, Thorndyke MC (1986) Insulin-like immunoreactivity in the neural ganglion of the ascidian Ciona intestinalis. Acta Zool 67:147–153CrossRefGoogle Scholar
  38. 38.
    Orci L (1984) Patterns of cellular and subcellular organization in the endocrine pancreas. J Endocrinol 102: 2–11CrossRefGoogle Scholar
  39. 39.
    Orci L, Stefan Y, Malaisse-Lagae F, Perrelet A (1979) Instability of pancreatic endocrine cell population throughout life. Lancet I: 615–616CrossRefGoogle Scholar
  40. 40.
    Polak JM, Van Noorden S (eds) (1986) Immunocytochemistry. Modern methods and applications, 2nd edn. Wright, Bristol, pp 1–736Google Scholar
  41. 41.
    Rahier J, Wallon J, Henquin JC (1981) Cell populations in the endocrine pancreas of human neonates and infants. Diabetologia 20: 540–546PubMedCrossRefGoogle Scholar
  42. 42.
    Rahier J, Fält K, Müntefering H, Becker K, Gepts W, Falkmer S (1984) The basic structural lesion of persistent neonatal hypoglycaemia with hyperinsulinism: deficiency of pancreatic D-cells or hyperactivity of B-cells? Diabetologia 26: 282–289PubMedCrossRefGoogle Scholar
  43. 43.
    Rose SR, Chrousos G, Cornblath M, Sidbury J (1986) Management of post-operative nesidioblastosis with zinc protamine glucagon and oral starch. J Pediatr 108: 97–100PubMedCrossRefGoogle Scholar
  44. 44.
    Scott J, Cowell J, Robertson ME, Priestley LM, Wadey R, Hopkins B, Pritchard J, Bell GI, Rall LB, Graham CF, Knott TJ (1985) Insulin-like growth factor-II gene-expression in Wilms’ tumour and embryonic tissues. Nature 317: 260–362PubMedCrossRefGoogle Scholar
  45. 45.
    Seifert G (1984) Congenital anomalies. Lipomatous atrophy and other forms. In: Klöppel G, Heitz PU (eds) Pancreatic pathology. Livingstone, Edinburgh, pp 22–31Google Scholar
  46. 46.
    Søvik O, Vidnes J, Falkmer S (1975) Persistent neonatal hypoglycemia. Acta Pathol Microbiol Scand (A) 83:155–166Google Scholar
  47. 47.
    Stefan Y, Falkmer S (1980) Identification of four endocrine cells types in the pancreas of Cottus scorpius (Teleostei) by immunofluorescence and electron microscopy. Gen Comp Endocrinol 42: 171–178PubMedCrossRefGoogle Scholar
  48. 48.
    Stefan Y, Ravazzola M, Orci L (1981) Primitive islets contain two populations of cells with differing glucagon immunoreactivity. Diabetes 30:192–195PubMedCrossRefGoogle Scholar
  49. 49.
    Stefan Y, Grasso S, Perrelet A, Orci L (1983) Quantitative immunofluorescent study of the endocrine cell population in the developing human pancreas. Diabetes 32: 293–307PubMedCrossRefGoogle Scholar
  50. 50.
    Stefan Y, Bordi C, Grasso S, Orci L (1985) Beckwith-Wiedemann syndrome: A quantitative, immunohistochemical study of pancreatic islet cell populations. Diabetologia 28: 914–919PubMedCrossRefGoogle Scholar
  51. 51.
    Thorndyke MC, Falkmer S (1985) Evolution of gastro-entero-pancreatic endocrine systems in lower vertebrates. In: Foreman RE, Gorbman A, Dodd JM, Olsson R (eds) Evolutionary biology of primitive fishes. Plenum, New York, pp 379–400Google Scholar
  52. 52.
    Titlbach M, Fält K, Falkmer S (1987) Ontogeny of the pancreatic islet parenchymal cells in the rabbit. An immunohistochemical and ultrastructural study with particular regard to the earliest appearance of argyrophil insulin-immunoreactive cells. Diabetes Res 5:105–117PubMedGoogle Scholar
  53. 53.
    Titlbach M, Fält K, Falkmer S (1985) Postnatal maturation of the islets of Langerhans in sheep. Light microscopic, immunohistochemical, morphometric, and ultrastructural investigations with particular reference to the transient appearance of argyrophil insulin immunoreactive cells. Diabetes Res 2: 5–15PubMedGoogle Scholar
  54. 54.
    Titlbach M, Chejfec G, Grimelius L, Falkmer S (1986) Neuroendocrine background of the pathology of the islets of Langerhans: A minireview with particular reference to synaptophysin and chromogranin A as neuroendocrine markers and to the ontogeny of argyrophil insulin immunoreactive cells in the rabbit. Exp Clin Endocrinol 89: 242–250CrossRefGoogle Scholar
  55. 55.
    Töpke B, Menzel K (1976) Die Pankreasagenesie des Neugeborenen, ein seltenes, klinisch aber charakteristisches Krankheitsbild. Acta Paediatr Acad Sci Hung 17:147–151PubMedGoogle Scholar
  56. 56.
    Van Noorden S (1984) The neuroendocrine system in protostomian and deuterostomian invertebrates and lower vertebrates. In: Falkmer S, Håkanson R, Sundler F (eds) Evolution and tumour pathology of the neuroendocrine system. Elsevier, Amsterdam, pp 7–38Google Scholar
  57. 57.
    Vance J, Stoll RW, Kitabchi AE, Williams RG, Wood FC (1969) Nesidioblastosis in familial endocrine adenomatosis. JAMA 207: 1679–1682PubMedCrossRefGoogle Scholar
  58. 58.
    Weibel ER (1973) Sterological techniques for electron microscopic morphometry. In: Hayat MA (ed) Principles and techniques of electron microscopy. Van Nostrand Reinhold, New York, pp 239–296Google Scholar
  59. 59.
    Wendel U, Kardorff C, Dorittke P, Bremer HJ (1985) Somatostatin in the treatment of neonatal persistent hypoglycemia due to hyper-insulinism (nesidioblastosis). Mschr Kinderhk 133: 527–531Google Scholar
  60. 60.
    Wöckel W, Scheibner K (1977) Aplasie des Pancreas mit Diabetes mellitus, intrahepatische Gallengangsaplasie und weitere Mißbildungen bei einem hypotrophen Neugeborenen. Z Pathol 121:186–194Google Scholar

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© Springer-Verlag Berlin Heidelberg 1988

Authors and Affiliations

  • S. Falkmer
  • U. Askensten

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