Riassunto
In alcune cavie immunizzate con una miscela insulina-adiuvante per ottenere sieri anti-insulina, sono state messe in evidenza caratteristiche lesioni nelle anse glomerulari del rene. Le pareti vasali sono apparse ispessite ed infiltrate da una sostanza mucopolisaccaridica PAS-positiva, depositata talora in noduli. Queste lesioni assomigliano a quelle della glomerulosclerosi diabetica. Nei casi più gravi è stato osservato un massivo accumulo di sostanza PAS-positiva, tale da deter-minare la parziale omogeneizzazione delle anse glomerulari. La sostanza PAS-positiva fissava l'insulina marcata con fluoresceina. L'esame al microscopio elettronico confermava l'esistenza di alterazioni simil-diabetiche negli animali trattati. Alterazioni analoghe non sono state riscontrate in nessuno degli animali di controllo. Tutte queste lesioni dimostrano l'esistenza di una reazione immune contro la miscela insulina-adiuvante. La possibilità di una patogenesi autoimmune dell'angiopatia diabetica viene discussa.
Resume
Les AA. ont observé des lésions caractéristiques dans les glomérules rénales des cobayes immunisées avec insuline plus «adjuvant» pour obtenir des sérums anti-insuline. Les parois vasculaires sont apparues épaisses et infiltrées par une substance muco-polysaccharidique PAS-positive, déposée parfois en nodules. Cettes lésions réssemblent à celles de la glomérulosclérose diabétique. Dans les cas plus graves on a observé une accumulation de la substance PAS-positive qui détermine une homogénisation des anses glomérulaires. La substance PAS-positive fixait l'insuline marquée avec fluorescine. L'examen au microscope éléctronique confirmait l'éxistence des altérations simildiabétiques chez les animaux traités. Des altérations analogues n'ont pas été observée chez les animaux de contrôle. Toutes cettes lésions démontrent l'éxistence d'une réaction immune contre l'insuline plus «adjuvant». On discute sur la possibilité d'une pathogenèse autoimmune de l'angiopathie diabétique.
Resumen
Al inmunizar conejos de india con un compuesto insulino-adyuvante, para obtener sueros antinsulina, se han puesto en evidencia lesiones carácterísticas en las asas glomerulares del riñón. Se pudo observar un mayor espesor en las paredes vasculares con infiltraciones de substancia mucopolisacárida PAS-positiva, depositada a veces en nódulos. Esas lesiones eran parecidas a las de la glomerulosclerosis diabética. En los casos más graves se pudo observar una acumulación masiva de substancia PAS-positiva, capaz de determinar la homogeneización parcial de las asas glomerulares. La substancia PAS-positiva fijaba la insulina marcada con fluorescina. El examen con el microscopio electrónico confirmaba la existencia de alteraciones semejantes a las diabéticas en los animales tratados. En ninguno de los animales de control se ha observado alteraciones análogas. Todas estas lesiones demuestran la existencia de una reacción inmune contra la combinación insulino-adyuvante. Se discute la posibilidad de una patogenesis autoinmune de la angiopatia diabética.
Zusammenfassung
Bei Immunisierung von Meerschweinchen mit einer Insulin-Adjuvansmischung fuer die Ausbeute von Anti-Insulinsera wurden charakteristische Schaeden der Glomerular-Knaeuel der Nieren festgestellt. Die Gefaesswaende zeitigten sich verdickt und mit einer PAS-positiven Mukopolysaccharid-Substanz infiltriert, die sich manchmal in Knoetchen ablagerte. Diese Schaeden sind denjenigen der diabetischen Glomerulosklerose aehnlich. Bei den schwergradigen Faellen wurde die massive Anhaeufung von PAS-positiver Substanz festgestellt, welche zum Teil die Homogenisierung der Glomerular-Knaeuel verursachte. Die PAS-positive Substanz fixierte das mit Fluoreszein markierte Insulin. Die Untersuchung am Elektronen-Mikroskop bestaetigte das Vorliegen von Diabetes-aehnlichen Veraenderungen bei den behandelten Tieren. Analoge Veraenderungen wurden bei keinem der Kontrolltiere beobachtet. All diese Schaeden beweisen eine Immunreaktion gegen die Insulin-Adjuvansmischung. Es wird die Moeglichkeit einer autoimmunen Pathogenese der diabetischen Angiopathie diskutiert.
Summary
When guinea pigs were immunized with an insulin-adjuvant mixture to obtain anti-insulin sera, peculiar lesions could be demonstrated in the glomerular tufts. The vascular walls were thickened, and infiltrations of PAS-positive mucopolysaccharide material, sometimes in the form of nodules, were observed. These changes were similar to those seen in diabetic glomerulosclerosis. In the most severe cases, a massive deposition of PAS-positive material was observed which had caused partial homogenization of the glomerular tufts. The PAS-positive material bound insulin labeled with fluorescein. Electron-microscopy examination confirmed the presence of diabetes-like vascular changes in the treated animals. Similar changes were absent in all control animals. These lesions indicate the existence of an immune reaction against the insulin-adjuvant mixture. The possibility of an autoimmune pathogenesis of diabetic angiopathy is discussed.
Bibliografia
Berns A. W., Owens C. T., Hirata Y., Blumenthal H. T.: The Pathogenesis of Diabetic Glomerulosclerosis. II. A Demonstration of Insulin-Binding Capacity of the Various Histopathological Components of the Disease by Fluorescence Microscopy - Diabetes11 308, 1962.
Berson S. A., Yalow R. S.: Some Current Controversies in Diabetes Research - Diabetes14 549, 1965.
Bloodworth J. M. B.: Ultrastructural Demonstration of Basic Similarities between Human Diabetic Glomerulosclerosis, Glomerulonephritis and Systemic Lupus Erythematosus - 25th Ann. Meet. ADA - Diabetes14 441, 1965.
Blumenthal H. T., Berns A. W., Owens C. T.: Insulin Antibodies - Lancet2 783, 1963.
Blumenthal H. T., Goldenberg S., Berns A. W.: The Pathology and Pathogenesis of the Disseminated Angiopathy of Diabetes Mellitus - Fifth Congress of IDF, Toronto, 1964. Excerpta Medica. International Congress Series74 253.
Blumenthal H. T., Goldenberg S., Berns A. W.: Pathology and Pathogenesis of the Disseminated Angiopathy of Diabetes Mellitus. In:Leibel B. S., Wrenshall G. A.: On the Nature and Treatment of Diabetes - Excerpta med. Found., Amsterdam, 1965, pag. 397.
Burnet MacFarlane: Experimental Production of Auto-Antibodies or of Auto-Immune Disease - Brit. med. Bull.19 245, 1963.
Camerini-Dávalos R. A.: Biochemical and Histological Aspects of Prediabetes. In:Leibel B. S., Wrenshall G. A.: On the Nature and Treatment of Diabetes - Excerpta med. Found., Amsterdam, 1965, pag. 657.
Chetty M. P., Watson K. C.: Antibody-Like Activity in Diabetic and Normal Serum Measured by Complement Consumption - Lancet1 67, 1965.
Deckert T.: Insulin Antibodies and Autoimmunization - Fifth Congress of IDF, Toronto, 1964. Excerpta Medica. International Congress Series74 168.
Farquhar M. C., Hopper J., Moon H. D.: Diabetic Glomerulosclerosis. Electron and Light Microscopic Studies - Amer. J. Path.35 721, 1959.
Grodsky G. M.: Production of Autoantibodies to Insulin in Man and Rabbits - Diabetes14 396, 1965.
Kimmelstiel P., Wilson C.: Intercapillary Lesions in the Glomeruli of the Kidney - Amer. J. Path.12 83, 1936.
Le Compte P. M.: «Insulitis» in Early Juvenile Diabetics - Arch. Path.66 450, 1958.
Lundbaeck K.: Nephropathy in Diabetic Subjects - In:Leibel B. S., Wrenshall G. A.: On the Nature and Treatment of Diabetes - Excerpta med. Found., Amsterdam, 1965, pag. 436.
Marble A., Rees S. B.: Die Pathophysiologie der Mikroangiopathie bei Diabetes - Triangel (De.)7 17, 1965.
Marshall J., Eveland W., Smith C.: Superiority of Fluorescein-Isothiocyanate for Fluorescent Technic with a Modification of Its Application - Proc. Soc. exp. Biol. (N.Y)98 898, 1958.
McDonald M. K., Ireland J. T.: The Glomerular Lesion in Idiopathic and Secondary Diabetes - Ciba Coll. Endocr.15 301, 1964.
Mohos S. Z., Hennigar G. R., Fogelman J. A.: Insulin-Induced Glomerulosclerosis in the Rabbit - J. exp. Med.118 657, 1963.
Páv J., Jezkova Z., Skrha F.: Insulin Antibodies - Lancet2 221, 1963.
Pencev I., Andreev D., Ditzov S.: Insulin-Precipitating Antibodies in Insulin-Treated and Untreated Diabetic Patients - Diabetologia4 164, 1968.
Rees S. B., Camerini-Dávalos R. A., Caulfield J. B., Lozano-Castañeda O., Cervantes-Amezcus A., Taton J., Pometta D., Krauthammer J. P., Marble A.: Pathophysiology of Microangiopathy in Diabetes Mellitus - Ciba Coll. Endocr.15 315, 1964.
Renold A. E.: Réactions immunologiques à l'injection d'insuline homologue et hétérologue -Journées de Diabétologie, Hôtel-Dieu, Flammarion, Paris 1965, pag. 25.
Renold A. E., Soeldner J. S., Steinke J.: Immunological Studies with Homologous and Heterologous Pancreatic Insulin in the Cow - Ciba Coll. Endocr.15 122, 1964.
Riggs J. L., Seiwald K., Dowus C.: Isothiocyanate Compounds as Fluorescent Labeling Agents for Immune Serum - Amer. J. Path.34 1081, 1958.
Spiro R. G.: Role of Insulin in Two Pathways of Glucose Metabolism; in Vivo Glucosamine and Glycogen Synthesis - Ann. N.Y. Acad. Sci.82 366, 1959.
Zampa G. A., Manzini A. M.: Kimmelstiel-Wilson-Like Nephropathy -Lancet2 300, 1965.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Andreev, D., Ditzov, S. & Dashev, G. Diabetes-like vascular lesions in the kidneys of guinea pigs immunized with an insulin-adjuvant mixture. Acta diabet. lat 7, 243–259 (1970). https://doi.org/10.1007/BF01556785
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF01556785