Summary
The gastro-intestinal mucosa of the rat has been systematically studied with the electron-microscope at the following levels: gastric fundus, pylorus, duodenum, jejunum and ileum. Two types of non-digestive epithelial cells have been observed, both exhibiting electron-dense granulations, both candidates for endocrine activity. The first type of cells contains round granules bearing remarkable similarity to the granules of pancreatic endocrine A cells. The second cell type is characterised by strikingly polymorphic granulations and would appear to correspond to the so-called enterochromaffine cells of light-microscopy. On the basis of this morphological criterion, and of the biochemical evidence suggesting the existence of a substance in the intestine which greatly resembles glucagon, biologically and immunologically, it is proposed that this substance is secreted by the first type of cells which resemble the pancreatic A cells.
Résumé
L'étude au microscope électronique de l'intestin de rat à différents niveaux: estomac, duodénum, jéjunum et iléon, permet d'observer 2 types de cellules à granulations denses. Le premier type, dont les granulations sont rondes, est semblable aux cellules A du pancréas. Le deuxième type de cellules, dont les granulations sont polymorphes, est associé aux cellules dites entérochromaffines. Sur la base de ce critère morphologique, et des données biochimiques affirmant l'existence dans l'intestin d'une substance biologiquement et immunologiquement proche du glucagon, il est proposé de situer la synthèse et sécrétion du glucagon intestinal au niveau de ces cellules endocrines intestinales de type A.
Zusammenfassung
Bei einer systematischen Untersuchung der Magen-Darm-Schleimhaut mit Hilfe des Elektronenmikroskopes wurden zwei Arten von besonderen Zellen in deren Epithelien festgestellt, die mögliche Träger endokriner Tätigkeit sind. Beide sind durch elektronenoptisch dunkle Granula gekennzeichnet. Der erste Typ enthält runde Einschlüsse, die den Sekret-Granula der endokrinen A-Zellen des Pankreas sehr ähnlich sind. Der zweite Zelltyp weist auffallend polymorphe Sekretgranula auf, die derjenigen der sogenannten enterochromaffinen Zellen im Lichtmikroskop entsprechen dürften. Diese morphologische Eigenschaft sowie die biochemischen Beobachtungen, welche auf das Vorhandenscin einer dem Glucagon biologisch und immunologisch ähnlichen Substanz im Darm deuten, lassen die Annahme zu, daß die den pankreatischen A-Zellen ähnlichen Zellen für die Sekretion des Darm-Glucagons verantwortlich sind.
Article PDF
Similar content being viewed by others
References
Caramia, F., B.L. Munger, andP.E. Lacy: The ultrastructural basis for identification of cell types in the pancreatic islets. I. Guinea pig. Z. Zellforsch.67, 533–566 (1965).
Cavallero, C., andE. Solcia: Cytological and histochemical aspects of islet pathology in the Zollinger-Ellison syndrome. Rev. Int. Hepat. XV,3, 517–526 (1965).
— —, andR. Sampietro: Cytology of islet tumours and hyperplasia associated with the Zollinger-Ellison syndrome. Gut8, 172–177 (1967).
Dunn, J.S., H.L. Sheehan, andN.G.M. Meletchie: Necrosis of islets of Langerhans produced experimentally. Lancet1943 I, 484–487.
Elfin, L.G.: The fine structure of the cell surface of chromaffin cells in the rat adrenal medulla. J. ultrastruct. Res.12, 263–286 (1965).
Erspamer, V., andB. Asero: Identification of enteramine the specific hormone of the enterochromaffin cell system as 5-hydroxytryptamine. Nature169, 800–801 (1959).
Forssmann, W., G. Siegrist, L. Orci, L. Girardier, R. Pictet, andCh. Rouiller: Fixation par perfusion pour la microscopic électronique. Essai de généralisation. J. Microscopie6, 279–304 (1967).
Forssmann, W., L.Orci, R.Pictet, and Ch.Rouiller: Zur Ultrastructur der endokrinen Zellen im Epithel des Magendarmtracts der Ratte. Comptes rendus de l'Union libre des Anatomistes des Universités suisses Bâle 1967 (sous presse).
Friend, D.S.: The fine structure of Brunner's glands in the mouse. J. cell. Biol.25, 563–576 (1965).
Gomori, G.: A new stain for elastic tissue. Amer. J. clin. Path.20, 665 (1950).
Gonet, A.E., andA.E. Renold: Homografting of fetal rat pancreas. Diabetologia1, 91–96 (1965).
Helander, H.F.: Ultrastructure of secretory cells in the pyloric gland area of the mouse gastric mucosa. J. ultrastruct. Res.10, 145–159 (1964).
Hellerstrom, C., B. Hellman, B. Petersson, andG. Alm: The two types of pancreatic A-cells and their relation to glucagon secretion. In: Symposium on the structure and metabolism of the pancreatic islet, p. 117–130. Eds.G.F. Brolin, B. Hellman, andH. Knutson. Oxford: Pergamon Press 1964.
Ito, S., andR.J. Winchester: The fine structure of the gastric mucosa in the bat. J. cell. Biol.16, 541–577 (1963).
Junod, A., A.E.Lambert, L.Orci, R.Pictet, A.E.Gonet, and A.E.Renold: Studies of the diabetogenic action of streptozotocin. Proc. Soc. exp. Biol. in press.
Karnovsky, M.J.: A simple method for staining with lead at high pH in electron microscopy. J. biophys. biochem. Cytol.11, 729–732 (1961).
Kenny, A.J., andR.R. Say: Glucagon-like activity extractable from the gastro-intestinal tract of man and other animals. J. Endocr.25, 1–7 (1962).
Lacy, P.E.: Electron microscopic identification of different cell types in the islets of Langerhans of the guinea pig, rat, rabbit and dog. Anat. Rec.128, 255–268 (1957).
Lee, D.-H.: Identification of argyrophilic cells in pancreatic islets by light and electron microscopy in osmium-fixed plastic-embedded sections. Z. Zellforsch.77, 1–7 (1967).
Leeson, C.R., andT.S. Leeson: The fine structure of Brunner's glands in the rat. Anat. Rec.156, 253–268 (1966).
Like, A.A., andE. Miki: Diabetic syndrome in sand rats. IV. Morphologic changes in islet tissue. Diabetologia3, 143–166 (1967).
Luft, J.H.: Improvements in Epoxy resin embedding methods. J. biophys. biochem. Cytol.9, 409–414 (1961).
Luse, S.A., andP.E. Lacy: Electron microscopy of a malignant argentaffin tumor. Cancer13, 334–346 (1960).
—,F. Caramia, G. Gerritsen, andW. Dulin: Spontaneous diabetes mellitus in the chinese hamster: an electron microscopic study of the islets of Langerhans. Diabetologia3, 97–108 (1967).
Manocchio, I.: The metachromatic A-cells in the pancreatic islets of dogs of different age. In: Symposium on the structure and metabolism of the pancreatic islets. Eds.G.F. Brolin, B. Hellman, andH. Knutson, p. 117–130. Oxford: Pergamon Press 1964.
Makman, M.H., andE.W. Sutherland: Use of liver adenyl cyclase for assay of glucagon in human gastrointestinal tract and pancreas. Endocrinology75, 127–134 (1964).
Melis, M., andL. Orci: La microscopia a contrasto di fase su ultrasezioni di tessuti e le sue applicazioni in biologia. Ric. Sci.34, Rend. B4, 365–410 (1964).
Merlini, D., andF.G. Caramia: Electron microscopic study of the cells of the human pancreatic islets. Rev. int. Hepat.16, 687–693 (1966).
Munger, B.L., F. Caramia, andP.E. Lacy: The ultrastructural basis for identification of cell types in the pancreatic islets. II. Rabbit, dog and opossum. Z. Zellforsch.67, 776–798 (1965).
Orci, L., W.G. Forssmann, R. Pictet, andCh. Rouiller: Mise en évidence des types de cellules à granulations denses dans le système digestif du rat. Société française de microscopie électronique. Colloque de Bruxelles, Mai 1967. J. Microscopie6, 74 a (1967).
Orci, L., R.Pictet, W.G.Forssmann, A.E.Renold, and Ch.Rouiller: Ultrastructural evidence for glucagon producing A-cells in the gastrointestinal mucosa of the rat. Proc. of the 6th congr. of the Internat. Diabetes Federation (1967).
Pictet, R., L. Orci, A.E. Gonet, Ch. Rouiller, andA.E. Renold: Ultrastructural studies of the hyperplastic islets of Langerhans of spiny mice (Acomys Cahirinus) before and during the development of hyperglycemia. Diabetologia3, 188–211 (1967).
Rennels, E.G.: An electron microscopy study of pituitary autograft cells in the rat. Endocrinology71, 713–722 (1962).
Samols, E., J. Tyler, C. Megyesi, andV. Marks: Immunochemical glucagon in human pancreas, gut and plasma. Lancet1966 II, 727–729.
Sedar, A.W., andM.H.F. Friedman: Correlation of the fine structure of the gastric parietal cell (Dog) with functional activity of the stomach. J. biophys. biochem. Cytol.11, 349–363 (1961).
—: The fine structure of the oxyntic cell in relation to functional activity of the stomach. Ann. N.Y. Acad. Sci.99, 9–29 (1962).
Solcia, E., G.Vassalo, and R.Sampietro: Endocrine cells in the antropyloric mucosa of the stomach. Z. Zellforsch, (in press).
Staley, M.V., andJ.S. Trier: Morphologic heterogeneity of mouse Paneth cell granules before and after secretory stimulation. Amer. J. Anat.117, 365–384 (1965).
Sutherland, B.W., andC. de Duve: Origin and distribution of the hyperglycemic-glycogenic factor of the pancreas. J. biol. Chem.175, 663–674 (1948).
Theret, C., andH. Renault: L'ultrastructure de tumeurs thyréotropes adenohypophysaires expérimentales après radiothyroïdectomie. Bull. Ass. franç. Cancer51, 505–534 (1964).
Turner, J.R., andW.G. Whaley: Intercisternal elements of the Golgi apparatus. Science147, 1303 (1965).
Unger, R.H., H. Ketterer, andA.M. Eisentraut: Distribution of immunoassayable glucagon in gastrointestinal tissues. Metabolism15, 865–867 (1966).
—,A. Eisentraut, K. Sims, M.S. McCall, andL.C. Madison: Sites of origin of glucagon in dogs and humans. Clin. Res.9, 53 (1961).
Young, B.A., C.L. Foster, andE. Cameron: Some observations on the ultrastructure of the adenohypophysis of the rabbit. J. Endocr.31, 279–287 (1965).
Zollinger, R.M., andE. Ellison: Primary peptic ulcerations of the jejunum associated with islet cell tumor of the pancreas. Ann. Surg.142, 709 (1955).
Author information
Authors and Affiliations
Additional information
Supported in part by grants No. 4237 and 3618 of the Fonds National Suisse de la Recherche Scientifique, Berne, Switzerland.
Rights and permissions
About this article
Cite this article
Orci, L., Pictet, R., Forssmann, W.G. et al. Structural evidence for glucagon producing cells in the intestinal mucosa of the rat. Diabetologia 4, 56–67 (1968). https://doi.org/10.1007/BF01241034
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF01241034