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The pancreatic islet system of the mouse (Mus musculus)

Ultrastructural report of six new cell types

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Summary

The pancreatic islet in the mouse has a highly complex and heterogeneous structure. It contains Aa, Ab, Ac, B, C, D, E, and F cells. The classification of cell types is primarily based on the shape, size and electron opacity of secretory granules and on the spatial relationship of the granules to their unit membranes. Morphological evidence is supported by a statistical analysis of the size distribution of granules and of their membranes. Experimental immunization of mice with insulin, provides additional data to support the existence of eight different cell types in the islet of the normal animal and reveales marked immunological stimulation of B cells, secondary stimulation of Aa, D and F cells, atrophy of Ac cells and hyperplasia of C cells. It is proposed that corresponding cell types exist in other mammals and man. The experimental insulin immunization process appears to perform an immunofunctional analysis of the islet, and suggests that in mice the Aa, D and F cells might be involved in cell energy supply. Lipocaic and some pancreatic factors with insulin-like activity (NSILA) will likely find their morphological equivalents. It is proposed that chemical solubility techniques represent the most promising avenues of approach to the isolation of secretory products from the endocrine pancreas, and that the assay of these extracts should primarily be conducted at the cell level.

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References

  • Angervall, L., C. Hellerström, and B. Hellman: Development of the endocrine pancreas of rats as manifested by the appearance of argyrophilia and granulation. Path. et Microbiol. 25, 389–399 (1962).

    Google Scholar 

  • Bänder, A.: Die Beziehung des 24 Stunden-Rhythmus vegetativer Funktionen zum histologischen Funktionsbild endocriner Drüsen. Z. exp. Med. 115, 229–250 (1950).

    Google Scholar 

  • Bargmann, W.: Die Langerhansschen Inseln des Pankreas. Handbuch der mikroskopischen Anatomie des Menschen, Bd. VI/2, S. 197–288 (hrsg. von W. V. Möllendorff). Berlin: Springer 1939.

    Google Scholar 

  • Batchelor, B. R.: Insulin-like activity. Diabetes 16, 418–434 (1967).

    Google Scholar 

  • Bencosme, S. A.: Studies on the methods of staining the islet cells of the pancreas. Arch. Path. 53, 87–97 (1952).

    Google Scholar 

  • —: Pancreatic islet cells. Need for a nomenclature of universal acceptance. In: Scientific Proc. Amer. Assoc. Pathol. and Bact. 1966. Amer. J. Path. 48, 49a-50a (1966).

    Google Scholar 

  • —, and E. Liepa: Regional differences of the pancreatic islet. Endocrinology 57, 588–593 (1955).

    Google Scholar 

  • —, and D. C. Pease: Electron microscopy of the pancreatic islet. Endocrinology 63, 1–13 (1958).

    Google Scholar 

  • Bennet, H. S., J. H. Luft, and J. C. Hampton: Morphological classification of vertebrate blood capillaries. Amer. J. Physiol. 196, 381–390 (1959).

    Google Scholar 

  • Bensley, R. R.: Studies on the pancreas of the guinea pig. Amer. J. Anat. 12, 297–388 (1911).

    Google Scholar 

  • Bensley, S. H., and C. A. Woerner: The effects of continuous intravenous injection of an extract of the alpha cells of the guinea pig pancreas on the intact guinea pig. Anat. Rec. 72, 413–433 (1938).

    Google Scholar 

  • Björkman, N., C. Hellerström, and B. Hellman: The ultrastructure of the islets of Langerhans in normal and obese-hyperglycemic mice. Z. Zellforsch. 58, 803–819 (1963).

    Google Scholar 

  • —: The cell types in the endocrine pancreas of the human fetus. Z. Zellforsch. 72, 425–449 (1966).

    Google Scholar 

  • Bloom, W.: New type of granular cell in islets of Langerhans of man. Anat. Rec. 49, 363–371 (1931).

    Google Scholar 

  • Bunnag, S., N. Warner, and S. Bunnag: Effect of alloxan on the mouse pancreas during and after recovery from diabetes. Diabetes 16, 83–89 (1967).

    Google Scholar 

  • Caramia, F.: Electron microscopic description of a third cell type in the islets of the rat pancreas. Amer. J. Anat. 12, 53–64 (1963).

    Google Scholar 

  • —, B. L. Munger, and P. E. Lacy: The ultrastructural basis for the identification of cell types in the pancreatic islets. I. Guinea pig. Z. Zellforsch. 67, 533–546 (1965).

    Google Scholar 

  • Cavallero, C., e E. Solcia: Considerazioni sulla citologia insulopancreatica; esistenza a possible funzione di un terzo tipo cellulare. Riv. Anat. pat. 24, 1000–1018 (1963).

    Google Scholar 

  • —, and R. Sampietro: Cytology of islet tumours and hyperplasias associated with the Zollinger-Ellison syndrome. Gut 8, 172–177 (1967).

    Google Scholar 

  • Coombs, R. E. A., and P. G. H. Gell: Diagnostic methods in serology and immunopathology. In: Clinical aspects of immunology (eds. P. G. H. Gell, and R. R. A. Coombs), p. 6–8. Oxford: Blackwell Scientific Publications 1963.

    Google Scholar 

  • Creutzfeldt, W.: Alpha cell cytotoxins. Their influence on carbohydrate metabolism and the effect of the oral blood glucose reducing sulfonamides on the islet cells. Diabetes 6, 135–145 (1957).

    Google Scholar 

  • Davidson, M. B., and Ch. J. Goodner: Failure of synalbumin to exhibit insulin antagonism in vivo. Diabetes 16, 386–394 (1967).

    Google Scholar 

  • Dragstedt, L. R., J. Van Prohaska, and H. P. Harms: Observations on a substance in pancreas (a fat metabolizing hormone) which permits survival and prevents liver changes in depancreatized dogs. Amer. J. Physiol. 117, 175–180 (1936).

    Google Scholar 

  • Elias, E., and A. Hennig: Stereology of the human renal glomerulus. In: Quantitative methods in morphology (eds. E. R. Weibel and H. Elias), p. 130–166. Berlin-Heidelberg-New York: Springer 1967.

    Google Scholar 

  • Fasske, E.: Lehrbuch der histologischen Technik. München und Berlin: Urban & Schwarzenberg 1964.

    Google Scholar 

  • Fernández-Morán, H., and R. Luft: Submicroscopic cytoplasmatic granules in the anterior lobe cells of the rat hypophysis as revealed by electron microscopy. Acta endocr. (Kbh.) 2, 199–211 (1949).

    Google Scholar 

  • Ferner, H.: Das Inselsystem des Pankreas. Stuttgart: Georg Thieme 1952.

    Google Scholar 

  • Froesch, E. R., W. A. Muller, H. Burgi, M. Waldvogel, and A. Labhart: NSILA of human serum. II. Biological properties of plasma extracts with non-suppressive ILA. Biochim. biophys. Acta (Amst.) 121, 360–370 (1966).

    Google Scholar 

  • Fuhrman, G. J., E. D. McLin, and M. L. Turner: The effect of time of the day on the metabolic rate of albino mice; a manometric method. Amer. J. Physiol. 147, 284–288 (1946).

    Google Scholar 

  • Fujita, T.: The identification of the agyrophil cells of pancreatic islets with D-cells. Arch. histol. jap. 25, 189–197 (1964).

    Google Scholar 

  • —: D-Zellen der Pankreasinseln beim Diabetes mellitus mit besonderer Berücksichtigung ihrer Argyrophilie. Z. Zellforsch. 69, 363–370 (1966).

    Google Scholar 

  • Georgsson, G., u. W. Wessel: Vergleichende elektronenmikroskopische Untersuchungen normaler menschlicher Pankreasinseln und eines hormonell-aktiven Inselzell-Carcinoma mit Hyperinsulinismus. Z. Krebsforsch. 69, 70–86 (1967).

    Google Scholar 

  • Gepts, W., Christophe, and J. Mayer: Pancreatic islets in mice with the obese hyperglycemic syndrome. Diabetes 9, 63–69 (1960).

    Google Scholar 

  • Gomori, G.: Studies on the cells of the pancreatic islets. Anat. Rec. 74, 439–459 (1939).

    Google Scholar 

  • —: Observations with differential stains on the human islets of Langerhans. Amer. J. Path. 17, 395–402 (1941).

    Google Scholar 

  • —: Pathology of the pancreatic islets. Arch. Path. 36, 217–232 (1943).

    Google Scholar 

  • —: Aldehyde-fuchsin: a new stain for elastic tissue. Amer. J. clin. Path. 20, 665–666 (1950).

    Google Scholar 

  • Grodsky, G. M., R. Feldman, W. E. Toreson, and J. C. Lee: Diabetes mellitus in rabbits immunized with insulin. Diabetes 15, 579–585 (1966).

    Google Scholar 

  • Gusek, W., u. J. Kracht: Elektronenmikroskopische Untersuchungen über Inselwachstum und acinoinsuläre Transformation. Frankfurt. Z. Path. 70, 98–106 (1959).

    Google Scholar 

  • Halmi, N. S., and J. Davies: Comparison of aldehyde-fuchsin staining, metachromasia and periodic acid-Schiff reactivity of various tissues. J. Histochem. Cytochem. 1, 447–453 (1953).

    Google Scholar 

  • Hansemann, D. Von: Über die Struktur und das Wesen der Gefäßinseln des Pankreas. Verh. dtsoh. path. Ges. 4, XXIV, 187–197 (1902).

    Google Scholar 

  • Harms, H.: Ein haltbares Aldehydfuchsin nach Gomori. Laboratoriums-Blätter 1, 7–13 (1954).

    Google Scholar 

  • Hellerström, C., and B. Hellman: The islets of Langerhans in yellow obese mice. Metabolism 12, 527–536 (1963).

    Google Scholar 

  • —, B. Petersson, and G. Alm: The two types of pancreatic A-cells and their relation to the glucagon secretion. In: The structure and metabolism of the pancreatic islets (eds. S. E. Brolin, B. Hellman and E. Knutson), p. 117–130. Oxford: Pergamon Press 1964.

    Google Scholar 

  • Hellman, B.: The occurrence of argyrophil cells in the islets of Langerhans of American obese-hyperglycemic mice. Acta endocr. (Kbh.) 36, 596–602 (1960).

    Google Scholar 

  • —, and C. Hellerström: The islets of Langerhans in ducks and chickens with special reference to argyrophil reaction. Z. Zellforsch. 52, 278–290 (1960).

    Google Scholar 

  • Herman, L., T. Sato, and P. J. Fitzgerald: The pancreas. In: Electron microscopic anatomy (ed. S. M. Kurtz), p. 59–95. New York and London: Academic Press 1964.

    Google Scholar 

  • Hoyos-Guevara, E. de: Die D-Zellen des Pankreas und ihre Bedeutung. Vortrag auf der 107. wissenschaftl. Sitzung der Berliner Gesellschaft für Pathologie am 14. 11. 67.

  • - The pancreatic D-cell. A cybernetic model applied to the problem of its functional significance. (In preparation, 1969).

  • - The morphology of the autoimmune diabetes in the mouse. (Unpublished observations.)

  • Jones, E. E.: Spontaneous hyperplasia of the pancreatic islets associated with glucosuria in hybrid mice. In: The structure and metabolism of the pancreatic islets (eds. S. E. Brolin, B. Hellman and H. Knutson), p. 189–192. Oxford: Pergamon Press 1964.

    Google Scholar 

  • Kalkhoff, R. K., and D. M. Kipnis: Studies of the metabolic effects of acute insulin deficiency. I. Mechanism of imparment of hepatic fatty acid and protein synthesis. Diabetes 15, 443–450 (1966).

    Google Scholar 

  • Lacy, P. E.: Electron microscopy of the normal islets of Langerhans. Diabetes 6, 498–507 (1957).

    Google Scholar 

  • Lane, M. A.: The cytological characters of the areas of Langerhans. Amer. J. Anat. 7, 409–422 (1907).

    Google Scholar 

  • Langerhans, P.: Beiträge zur Mikroskopischen Anatomie der Bauchspeicheldrüse. Dissertation Berlin 1869.

  • Lazarow, A.: Cell types of the islets of Langerhans and the hormones they produce. Diabetes 6, 222–231 (1957).

    Google Scholar 

  • Lazarus, S. S., and B. W. Volk: The pancreas in human and experimental diabetes. New York and London: Grune & Stratton 1962.

    Google Scholar 

  • LeCompte, P. M., J. Steinke, J. S. Soeldner, and A. E. Renold: Changes in the islets of Langerhans in cows injected with heterologous and homologous insulin. Diabetes 15, 586–596 (1966).

    Google Scholar 

  • Lillie, R. D.: Histopathologic technic and practical histochemistry, 3rd ed., p. 537–538. New York: McGraw-Hill Book. Co. 1965.

    Google Scholar 

  • Logothetopoulos, J.: Electron microscopy of the pancreatic islets of the rat. Effects of prolonged insulin injections. Diabetes 15, 823–829 (1966b).

    Google Scholar 

  • —, and E. G. Bell: Histological and autoradiographic studies of the islets of mice injected with insulin antibody. Diabetes 15, 205–211 (1966a).

    Google Scholar 

  • —, J. K. Davidson, R. E. Haist, and C. H. Best: Degranulation of B-cells and loss of pancreatic insulin after infusions of insulin antibody or glucose. Diabetes 14, 493–500 (1965).

    Google Scholar 

  • Manocchio, I.: Metachromatische Färbung der A-Zellen in Pankreasinseln von Canis familiaris. Zbl. allg. Path. path. Anat. 101, 1–4 (1960).

    Google Scholar 

  • —, e F. Caramia: Metacromasia e cellule alfa nelle isole pancreatiche di uomo. Sperimentale 112, 1–27 (1962).

    Google Scholar 

  • McManus, J. F. A., and R. W. Mowry: Staining methods. Histologic and histochemical, p. 126–128. New York: Harper & Row 1963.

    Google Scholar 

  • Meek, J. C., K. M. Doffing, and R. E. Bolinger: Radioimmuno-assay of insulin. A and B chains in normal and diabetic human plasma. Diabetes 17, 61–66 (1968).

    Google Scholar 

  • Michel, H.: Papierchromatographische Darstellung von Insulinantikörpern. Kongreßber. 5. Europ. Allergie-Kongr., Basel 1962. Selbstverlag Schweiz. Allergie-Ges. p. 351–353 (1963).

  • —: Vergleichende serologische, papierchromatographische und immunoelektrophoretische Untersuchungen über zirkulierende Insulin-Antikörper. Gastroenterologia (Basel), Suppl. 104, 188–191 (1965).

    Google Scholar 

  • Mohnike, G., G. Holle u. V. Moritz: Untersuchungen am Inselorgan der weißen Maus. I. Mitt. Verhalten der Granula der B-Zellen nach Natriumdiäthyldithiocarbamat. Endokrinologie 43, 166–172 (1962a).

    Google Scholar 

  • —: Untersuchungen am Inselorgan der weißen Maus. II. Mitt. Über die Beeinflussung des Granula-Bildes am Langerhansschen Organ der weißen Maus unter Dextrose und Insulingabe. Endokrinologie 43, 173–185 (1962b).

    Google Scholar 

  • —: Untersuchungen am Inselorgan der weißen Maus. III. Mitt. Über die Beeinflussung des Granula-Bildes der B-Zellen des Langerhansschen Organs der weißen Maus unter Laevulose. Endokrinologie 43, 185–189 (1962c).

    Google Scholar 

  • —: Untersuchungen am Inselorgan der weißen Maus. IV. Mitt. Über die Beeinflussung des Granula-Bildes der B-Zellen des Langerhansschen Organs der weißen Maus durch N-Sulfanilyl-N′-Butylharnstoff. Endokrinologie 43, 190–197 (1962d).

    Google Scholar 

  • —, and V. Moritz: On the nuclear size and the histochemistry of the B-cells in mice subjected to various experimental conditions. In: The structure and metabolism of the pancreatic islets (eds. S. E. Brolin, B. Hellman, and H. Knutson), p. 75–81. Oxford: Pergamon Press 1964.

    Google Scholar 

  • Munger, B. L.: A light and electron microscopic study of cellular differentiation in the pancreatic islets of the mouse. Amer. J. Anat. 103, 275–311 (1958).

    Google Scholar 

  • —, F. Caramia, and P. E. Lacy: The ultrastructural basis for the identification of cell types in the pancreatic islets. II. Rabbit, dog and opossum. Z. Zellforsch. 67, 776–798 (1965).

    Google Scholar 

  • Nakamura, M.: Cytological and histological studies on the pancreatic islets of a diabetic strain of the mouse. Z. Zellforsch. 65, 340–349 (1965).

    Google Scholar 

  • Orci, L., R. Pictet, W. G. Forssman, A. E. Renold, and Ch. Roviller: Structural evidence for glucagon producing cells in the intestinal mucosa of the rat. Diabetologia 4, 56–67 (1968).

    Google Scholar 

  • Pictet, R., L. Orci, A. E. Gonet, Ch. Rovoller, and A. E. Renold: Ultrastructural studies of the hyperplastic islets of Langerhans of spiny mice (Acomys cahirinus) before and during the development of hyperglycemia. Diabetologia 3, 188–211 (1967).

    Google Scholar 

  • Randle, P. J., C. N. Hales, P. B. Garland, and E. A. Newsholme: The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1963I, 785–789.

  • Robertson, J. D.: Unit membranes: a review with recent new studies of experimental alterations and a new subunit structure in synaptic membranes. In: Cellular membranes in development (ed. M. Locke), p. 1–81. New York and London: Academic Press 1964.

    Google Scholar 

  • Robertson, J. S.: A morphological study with the electron microscope of sections of normal mouse pancreas. Aust. J. exp. Biol. med. Sci. 32, 229–234 (1954).

    Google Scholar 

  • Rodbell, M.: Metabolism of isolated fat cells. I. Effects of hormones on glucose metabolism and lipolysis. J. biol. Chem. 239, 375–380 (1964).

    Google Scholar 

  • Romeis, B.: Mikroskopische Technik. München: Leibniz, R. Oldenbourg 1948.

    Google Scholar 

  • Saguchi, S.: Cytological studies of Langerhans' islets, with special reference to the problem of their relation to the pancreatic acinus tissue. Amer. J. Anat. 28, 1–58 (1920–1921).

    Google Scholar 

  • Schiebler, T. H., u. S. Schiessler: Über den Nachweis von Insulin mit den metachromatisch reagierenden Pseudoisocyaninen. Histochemie 1, 445–465 (1959).

    Google Scholar 

  • Solcia, E., and R. Sampietro: On the nature of the metachromatic cells of pancreatic islets. Z. Zellforsch. 65, 131–138 (1965).

    Google Scholar 

  • Steiner, D. F., and P. E. Oyer: The biosynthesis of insulin and probable precursor of insulin by a human islet cell adenoma. Proc. nat. Acad. Sci. (Wash.) 57, 473–480 (1967).

    Google Scholar 

  • Stolpmann, H. J.: Die postkapillären Venen im postnatalen Mäuselymphknoten. Vortrag auf der 91. wissenschaftl. Sitzung der Berliner Gesellschaft für Pathologie, 9. 3. 1965.

  • Thiel, A.: Über die Pankreasinseln normaler und diabetischer Fettmäuse. Verh. anat. Ges. (Jena) 105, 251–258 (1958).

    Google Scholar 

  • Thomas, T.: Cellular components of the mammalian islets of Langerhans. Amer. J. Anat. 62, 31–58 (1937).

    Google Scholar 

  • Toker, C.: Observations on the ultrastructure of a metastasizing beta cell islet tumor. Diabetes 16, 800–803 (1967).

    Google Scholar 

  • Toreson, W. E., J. C. Lee, and G. M. Grodsky: The histopathology of immune diabetes in the rabbit. Amer. J. Path. 52, 1099–1115 (1968).

    Google Scholar 

  • Unger, R. H., and A. M. Eisentraut: Glucagon. In: Hormones in blood (eds. Ch. Gram and A. L. Bachard), 1st ed., chapt. V. London and New York: Academic Press 1967.

    Google Scholar 

  • Volk, B. W., M. G. Goldner, and H. Frank-Crowley: The effect of prolonged growth hormone administration on the pancreatic alpha cells in normal and hypophysectomized rats. Use of a modification of Davenport's silver impregnation method. Metabolism 4, 491–502 (1955).

    Google Scholar 

  • Wang, S., and F. H. Carpenter: A compositional assay for insulin applied to a search for “proinsulin”. J. biol. Chem. 240, 1619–1625 (1965).

    Google Scholar 

  • Wolter, B.: Die Langerhansschen Inseln des Pferdes mit besonderer Berücksichtigung der Zelltypen. Z. Zellforsch. 35, 229–239 (1950).

    Google Scholar 

  • Wrenshall, G. A., S. B. Andrus, and J. Mayer: High levels of pancreatic insulin coexistence with hyperglycemia and degranulation of Beta cells in mice with the hereditary obese-hyperglycemic syndrome. Endocrinology 56, 335–340 (1954).

    Google Scholar 

  • Zagury, D., J. De Brux, J. Adgla et L. Leger: Etude des îlots de Langerhans du pancréas humain au microscope électronique. Presse méd. 69, 887–890 (1961).

    Google Scholar 

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    Evelio de Hoyos-Guevara

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Dedicated to Prof. Dr. med. W. Masshoff on his 60th birthday.

The author is indebted to Dr. med. H. J. Stolpmann for guidance in applying the techniques of electron microscopy and wishes to express his special appreciation to Mrs. Marjanne Hinz for her valuable assistance in completing different aspects of this work and for her competent technical aid.

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de Hoyos-Guevara, E. The pancreatic islet system of the mouse (Mus musculus). Z. Zellforsch. 101, 28–62 (1969). https://doi.org/10.1007/BF00335584

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