Summary
Glomeruli and tubules of the kidney of normoglycemic and diabetic spiny mice were studied with the electron microscope. Progressive thickening of the basement membranes of glomerular capillaries with a concomitant increase in the deposition of basement-membrane-like mesangial matrix occurred with age. Focal hemispherical thickenings of the basement membrane on its epithelial side were observed with increasing frequency in older animals. The plasma membrane of adjacent foot processes exhibited features suggestive of pinocytosis. Collagen fibers in electronlucent areas surrounded by mesangial matrix were regularly seen in animals beyond the age of twelve months. In diabetic animals, the alterations of the glomerular capillary basement membranes and of the mesangial region appeared to be more pronounced but no specific lesions were observed. This negative finding may be related to the relatively short duration of the diabetic state. Measurements of the thickness of glomerular capillary basement membranes showed a significant age-dependent increase in basement membrane width and indicated that this process may be accelerated in diabetic animals. Examination of the renal tubules of diabetic animals showed a characteristic segmental pattern of glycogen storage in epithelial cells with considerable variations in the degree of glycogen infiltration between different segments but also between individual cells of a given segment. The most surprising feature associated with glycogen storage was the occurrence of lysosomes filled with glycogen. The mechanisms responsible for the accumulation of glycogen within lysosomes are unknown but may be related to an increase in glycogen turnover in cells actively involved in the reabsorption of glucose or to an impairment of lysosomal function secondary to diabetes.
Résumé
Les glomérules et tubules rénaux de souris à piquants (Acomys cahirinus) normoglycémiques et diabétiques ont été étudiés au microscope électronique. L'épaisseur de la membrane basale des capillaires glomérulaires ainsi que l'espace occupé par la matrice mésangiale augmentaient progressivement avec l'âge de l'animal. Outre l'épaississement général de la membrane basale, on nota un épaississement focal du côté épithélial. La membrane cytoplasmique des prolongements podocytaires adjacents présentaient des modifications suggérant une pinocytose active. Chez les animaux âgés de plus de douze mois, la matrice mésangiale était régulièrement caractérisée par la présence de lacunes contenant des fibres de collagène. Chez les animaux diabétiques, les altérations capillaires et mésangiales étaient en général plus marquées sans que l'on ait rencontré les lésions typiques du diabète. Ceci pourrait être dû à la durée relativement brève du diabète chez les animaux examinés. L'épaisseur des membranes basales des capillaires glomérulaires augmente progressivement avec l'âge et le diabète pourrait accélérer ce processus. L'examen des tubules rénaux des animaux diabétiques a permis de constater que le degré d'infiltration de glycogène varie de façon caractéristique entre les différents segments tubulaires, mais aussi entre les cellules épithéliales d'un même segment. La présence de lysosomes remplis de glycogène représente l'observation la plus surprenante. Les mécanismes responsables de cette accumulation intralysosomiale de glycogène sont encore inconnus: elle peut résulter de la réabsorption massive de glucose et/ou d'un dérangement de la fonction lysosomiale secondaire à l'état diabétique.
Zusammenfassung
Die Glomeruli und Tubuli der Nieren normoglykämischer und diabetischer Stachelmäuse (Acomys cahirinus) wurden untersucht: Die Basalmembranen der Glomeruluskapillaren sowie die Matrix des Mesangiums verdickten sich mit zunehmendem Alter der Tiere; weiterhin ließen sich bei älteren Tieren fokale Verbreiterungen auf der epithelialen Seite der Basalmembran nachweisen, die ultrastrukturell von der letztern nicht zu unterscheiden waren. Die Plasmamembran der angrenzenden Podocytenfüßchen enthielt auf gesteigerte Mikropinocytose hinweisende Vesikel. In der Matrix des Mesangiums von über zwölf Monate alten Tieren fanden sich regelmäßig Lacunen, in denen Kollagenfasern festgestellt wurden. Bei diabetischen Tieren waren die Veränderungen der Basalmembranen und des Mesangiums in der Regel stärker ausgeprägt als bei normoglykämisehen; sogenannte typische diabetische Veränderungen wurden aber nicht beobachtet. Dies mag mit der relativ kurzen Dauer des Diabetes der untersuchten Tiere zusammenhängen. Die Messung der Dicke der Basalmembranen der Glomeruluskapillaren ergab daß diese mit steigendem Alter zunimmt und daß diese Verdickung bei diabetischen Tieren möglicherweise beschleunigt verläuft. In den Tubuli derselben diabetischen Tiere wurde eine charakteristische segmentäre Verteilung der Glykogenspeicherung beobachtet, dabei schwankte aber die Intensität der Glykogenspeicherung auch innerhalb eines Segments von Zelle zu Zelle. Das auffallendste im Zusammenhang mit der Glykogenspeicherung beobachtete Phänomen waren mit Glykogen angefüllte Lysosomen. Wie es zu dieser lysosomialen Glykogenspeicherung kommt, ist noch unbekannt; der erhöhte Anfall von Glucose (Reabsorption) und/oder eine durch den Diabetes bedingte Störung lysosomialer Funktionen kommen als ursächliche Faktoren in Frage.
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References
Alousi, M.A., Post, R.S., Heymann, W.: Experimental autoimmune nephrosis in rats. Amer. J. Path.54, 47–71 (1969).
Andrew, W., Pruett, D.: Senile changes in the kidneys of Wistar Institute rats. Amer. J. Anat.100, 51–69 (1957).
Ashworth, C.T., Erdmann, R.R., Arnold, N.J.: Age changes in the renal basement membrane in rats. Amer. J. Path.36, 165–179 (1960).
Baudhuin, P., Hers, H.G., Loeb, H.: An electron microscopic and biochemical study of type II glycogenosis. Lab. Invest.13, 1139–1152 (1964).
Bencosme, S.A., Stone, R.S., Latta, H., Madden, S.C.: Acute reactions with collagen production in renal glomeruli of rats as studied electron microscopically. J. Ultrastructure Res.3, 171–185 (1959).
Biava, C., Grossman, A., West, M.: Ultrastructural observations on renal glycogen in normal and pathologic human kidneys. Lab. Invest.15, 330–356 (1966).
Blumenthal, H.T., Hirata, Y., Owens, C.T., Berns, A.W.: A histo- and immunologic analysis of the small vessel lesion of diabetes in the human and in the rabbit. In: Small blood vessel involvement in diabetes mellitus, p. 279–287, Siperstein, M.A. (Ed.). Washington, D.C.: Am. Inst. Biological Sciences 1964.
Comerford, F.R., Cohen, A.S., Desai, R.G.: The evolution of the glomerular lesion in NZB mice. Lab. Invest.19, 643–651 (1968).
Coulfield, J.B.: cited by [8].
Drochmans, P.: Morphologie du glycogène. Etude au microscope électronique de colorations négatives du glycogène particulaire. J. Ultrastructure Research6, 141–163 (1962).
Froesch, E.R., Ashmore, J., Renold, A.E.: Comparison of renal and hepatic effects of fasting, cortisone administration and glucose infusion in normal and adrenalectomized rats. Endocrinology62, 614–620 (1958).
Garancis, J.C.: Type II glycogenosis. Biochemical and electron microscopic study. Amer. J. Med.44, 289–300 (1968).
Gonet, A.E., Stauffacher, W., Pictet, R., Renold, A.E.: Obesity and diabetes mellitus with striking congenital hyperplasia of the islets of Langerhans in spiny mice (Acomys cahirinus). I. Histological findings and preliminary metabolic observations. Diabetologia1, 162–171 (1965).
Gude, W. D., Upton, A.C.: A histologic study of spontaneous glomerular lesions in aging RF mice. Amer. J. Path.40, 699–709 (1962).
Guttman, P.H., Andersen, A.C.: Progressive intercapillary glomerulosclerosis in aging and irradiated beagles. Radiat. Res.35, 45–60 (1968).
—, Kohn, H.I.: Progressive intercapillary glomerulosclerosis in the mouse, rat and Chinese hamster, associated with aging and X-ray exposure. Amer. J. Path.37, 293–307 (1960).
Hers, H.G.: Inborn lysosomal diseases. Gastroenterology48, 625–633 (1965).
Jézéquél, A.-M., Arakawa, K., Steiner, J.W.: The fine structure of the normal, neonatal mouse liver. Lab. Invest.14, 1894–1930 (1965).
Jørgénsén, F.: éléctron microscopic studiés of normal glomémlar basémént mémbrané. Lab. Invést.17, 416–424 (1967).
Junod, A., Orci, L., Renold, A.E.: Lésions morphologiqués et physiologiques dans le syndrome complexe des souris à piquants (Acomys cahirinus). In: Journées annuelles de diabétologie de l'Hôtel-Dieu, Paris, p. 31–39. Paris: Ed. Médicales Flammarion 1968.
—, Letarte, J., Lambert, A. E., Stauffacher, W.: Studies in spiny mice (Acomys cahirinus): Metabolic state and pancreatic insulin releasein vitro. Horm. Metab. Res.1, 45–52 (1969).
Karnovsky, M.J.: Simple methods for “staining with lead” at high pH in electron microscopy. J. biophys. biochem. Cytol.11, 729–732 (1961).
Kefalides, N. A.: Characterization of the collagen from lens capsule and glomerular basement membranes. In: Diabetes, p. 307–322, J. Östman (Ed.). Amsterdam: Excerpta Medica Foundation 1969.
Kimmelstiel, P., Wilson, C.: Intercapillary lesions in the glomeruli of the kidney. Amer. J. Path.12, 83–97 (1936).
Kohn, H.I., Guttman, P.H.: Life span, tumor incidence and intercapillary glomerulosclerosis in the Chinese hamster (Cricetulus griseus) after whole-body and partial-body exposure to X-rays. Radiat. Res.21, 622–643 (1964).
Kurz, S.M., Feldman, J.D.: Experimental studies on the formation of the glomerular basement membrane. J. Ultrastructure Res.6, 19–27 (1962).
Latta, H.: Collagen in normal rat glomeruli. J. Ultrastructure Res.5, 364–373 (1961).
Luft, J.H.: Improvement in Epoxy-resin embedding methods. J. biophys. biochem. Cytol.9, 409–414 (1961).
Millonig, G.: Advantages of a phosphate buffer for OsO4 solutions in fixation. J. appl. Physiol.32, 1637–1640 (1961).
Peach, R., Williams, G.: Collagen in normal mouse glomeruli. Nature211, 1099 (1966).
Phillips, M.J., Unaker, N.J.: Glycogen depletion in the newborn rat liver. An electron microscopic and electron histochemical study. J. Ultrastructure Res.18, 142 -165 (1967).
Pictet, R., Orci, L., Gonet, A.E., Rouiller, Ch., Renold, A.E.: Ultrastructural studies of the hyperplastic islets of Langerhans of spiny mice (Acomys cahirinus) before and during the development of hyperglycemia. Diabetologia3, 188–211 (1967).
Ritchie, S., Waugh, D.: The pathology of Armanni-Ebstein diabetic nephropathy. Amer. J. Path.33, 1035–1057 (1957).
Robbins, S.L.: The reversibility of glycogen nephrosis in alloxan-treated diabetic rats. Amer. J. med. Sci.219, 376–381 (1950).
Shirai, T., Welsh, 3rd, G.W., Sims, E.A.H.: Diabetes mellitus in the Chinese hamster. II. The evolution of renal glomerulopathy. Diabetologia3, 266–286 (1967).
Siperstein, M.A., Unger, R.H., Madison, L.L.: Studies of muscle capillary basement membranes in normal subjects, diabetic and prediabetic patients. J. clin. Invest.47, 1973–1999 (1968).
Spicer, S.S.: Histological localization of glycogen in the urinary tract and lung. J. Histochem. Cytochem.6, 52–60 (1958).
Spiro, R.G.: Glycoproteins: Biochemistry, biology and role in disease. New Engl. J. Med.281, 991–1001, and 1043–1056 (1969).
Stauffacher, W., Orci, L., Amherdt, M., Lambert, A.E., Renold, A.E., Rouiller, Ch.: Le diabète spontané chez l'animal: Considérations sur la pathogénèse du syndrome aigu et sur la morphologie des lésions du syndrome chronique. Pathologie et Biologie (Paris)18, 539–549, (1970).
- - - Burr, I.M., Balant, L., Froesch, E.R., Renold, A.E.: Metabolic state, pancreatic insulin content and B-cell morphology of normoglycemic spiny mice (Acomys cahirinus): Indications for an impairment of insulin secretion. Diabetologia, this issue.
Warren, S., Root, H.F.: The pathology of diabetes, with special reference to pancreatic regeneration. Amer. J. Path.1, 415–429 (1925).
Witzleben, C.L.: Renal cortical tubular glycogen localization in glycogenosis type II (Pompe's disease). Lab. Invest.20, 424–429 (1969).
Yamada, E.: Collagen fibrils within the renal glomerulus. J. biophys. biochem. Cytol.7, 407–409 (1960).
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Supported in part by the Fonds National Suisse de la Recherche Scientifique, Berne, Switzerland (Grants No. 5344 and 4848.3), and by a grant-in-aid through Zyma S.A., Nyon, Switzerland.
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Orci, L., Stauffacher, W., Amherdt, M. et al. The kidney of spiny mice (Acomys cahirinus): Electron microscopy of glomerular changes associated with ageing and tubular glycogen accumulation during hyperglycemia. Diabetologia 6, 343–355 (1970). https://doi.org/10.1007/BF01212248
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DOI: https://doi.org/10.1007/BF01212248