Summary
Successful homografts of fetal rat pancreas into the testis of adult alloxan diabetic rats have been obtained in approximately 20% of a large series of experiments. Success was defined by graft survival over periods of 3 weeks or more, with evidence of multiplication of the transplanted endocrine cells. Histologic examination has demonstrated the existence of 3 morphological types of grafts 1. solid grafts; 2. scattered islet grafts; 3. pseudo-canalicular grafts. The endocrine cells were predominantly of the B type and typical β granulations could be demonstrated in all types with appropriate stains. Furthermore, acid ethanol extracts of the grafts exhibited considerable insulin-like activity on rat epididymal adipose tissue, activity which was completely suppressed by the addition of anti-insulin serum. The insulin content varied between 5 and 1200 units per gram and thus approached, in the solid grafts, the theoretical level for pure B cells. Although there was some suggestive evidence in favour of endocrine function of the graft within the host, the data are not as yet sufficient to establish this fact. Additional experiments will be needed and are in progress.
Résumé
Il est possible de faire des homogreffes de pancréas de rat foetal dans le testicule de rats adultes diabétiques, et d'obtenir dans les 20% des cas la survie et la multiplication des cellules endocrines implantées. L'étude histologique a montré trois types morphologiques de greffon: 1. les greffons solides, 2. en îlots disséminés, 3. de type pseudo-canaliculaire. Les colorations histologiques, telles l'aldéhyde-thionine mettent en évidence des granulations intracytoplasmiques semblables aux granulations β des cellules B de Langerhans. Le dosage biologique sur le tissu adipeux épididymaire du rat met en évidence une activité insulinique du greffon pouvant varier de 5 à 1200 UI d'insuline par gramme. Cette activité insulinique est entièrement supprimable par le sérum anti-insulinique. Les auteurs analysent les rapports qui existent entre la présence des granulations β et l'activité insulinique dans les homogreffes pancréatiques; mais ils ne peuvent pas encore répondre à la question capitale: le greffon est-il ou n'est-il pas fonctionnel. La réponse sera probablement donnée par une expérimentation similaire, actuellement en cours, mais effectuée cette fois, chez les rats consanguins, ce qui permet d'espérer un taux très élevé de reprises des isogreffes et des études statistiques suffisantes.
Zusammenfassung
Erfolgreiche intratestikuläre Homotransplantationen foetalen Rattenpankreasgewebes ließen sich in etwa 20% der Versuche bei Alloxan-diabetischen Ratten durchführen. Als Kriterium für die erfolgreiche Implantation galt das Überleben der Transplantate über drei Wochen oder länger mit nachweisbarer Vermehrung der innersekretorischen Zellen. Auf Grund des histologischen Bildes lassen sich die Transplantate in 3 Typen unterteilen: 1. kompakte, 2. inselförmige und 3. pseudo-canaliculäre. Die innersekretorischen Zellen sind bei allen drei Typen fast ausschließlich β-Zellen mit typischen β-Granula, die histochemisch charakteristisch reagieren. Außerdem ließ sich in salzsauren Äthanolextrakten der Transplantate am Rattenfettgewebe meßbare Insulinähnliche Aktivität nachweisen. Diese Insulin-ähnliche Aktivität verschwand bei Zusatz von Anti-Insulin Serum vollständig. Der Insulingehalt betrug zwischen 5 und 1200 Einheiten pro Gramm Transplantat und entsprach somit in einzelnen kompakten Transplantaten nahezu dem theoretischen Insulingehalt reiner β-Zellpräparate. Obschon bei den diabetischen Trägern der Transplantate Hinweise auf deren innersekretorische Aktivität beobachtet wurden, genügen die bisherigen Resultate nicht für eine beweisende Dokumentation. Zusätzliche Experimente sind im Gange.
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References
Gonet, A.B.: Correction du diabète expérimental du rat par la greffe pancréatique foetale, Acta Endocr. (Kbh) supplementing 62, 38 (1961).
- Studies on transplantation of fetal rat pancreas. In Proceedings of the 3rd International Symposium, Stockholm, 1963; Pergamon Press: The Structure and Metabolism of the Pancreatic Islets, p. 179 (1964).
Eagle, H.: Nutrition needs of mammalian cells in tissue culture. Science, 122, 501 (1955).
Renold, A.E., D.B. Martin, Y.M. Dagenais, J. Steinke, R. J. Nickerson, and M. C. Sheps: Measurement of small quantities of insulin-like activity using rat adipose tissue. I. A proposed procedure. J. Clin. Invest., 39, 1487 (1960).
Steinke, J., J. Soeldner, and A.E. Renold: Measurement of small quantities of insulin-like activity with rat adipose tissue. IV. Serum insulin-like activity and tumor insulin content in patients with functioning islet-cell tumors. J. Clin. Invest. 42, 1322 (1963).
Gomori, G.: A new stain for elastic tissue. Am. J. Clin. Pathol., 20, 665 (1950), used according to Wilson's modification, personal communication from Dr. W. Creutzfeldt, Göttingen.
Ivic, M.: Neue selektive Färbungsmethode der A- und B-Zellen der Langerhansschen Inseln. Anat. Anz., 107, 347 (1959).
Paget, G.E.: Aldehyde-Thionin: a stain having similar properties to Aldehyde-Fuchsin. Stain. Techn., 34, 223 (1959).
Dixit, P.K., I.K. Lowe, C.B. Heggestad, and A. Lazarow: Insulin content of microdissected fetal islets obtained from diabetic and normal rats. Diabetes 13, 71 (1964).
Davidson, J.K., R.E. Haist, and C.H. Best: Studies employing a new method for the recovery of biologically active insulin from acid alcoholic extracts of pancreas and blood serum. Diabetes, 12, 448 (1963).
Haist, R.E.: Islet cell function. Ann. N. Y. Acad. Sci. 82, 266 (1959).
Lacy, P.E., and J.R. Williamson: Quantitative histochemistry of the islets of Langerhans. II. Insulin content of dissected beta cells. Diabetes, 11, 101 1962).
Ferner, H.: Das Inselsystem des Pankreas. Georg Thieme Verlag. Stuttgart, p. 120 (1952).
Patel, J., G. Wajcner, and J.M. Cormier: Adénomes Langerhansiens hypoglycémiants: données chirurgicales et anatomo-pathologiques. Presse Méd., 73, 223 (1965).
Porter, M.R., and V.K. Frantz: Tumors associated with hypoglycemia, pancreatic and extrapancreatic. Am. J. Med., 21, 944 (1956).
Benscome, S.A., R.A. Allen, and H. Latta: Functioning pancreatic islet cell tumors, studied electronmicroscopically. Am. J. Path. 42, 1 (1963).
House, E.L., C. Burton, H. Cooper, and E. Anderson: The implantation of neonatal pancreas into the cheek pouch of the alloxan diabetic hamster. Endocrinology, 63, 389 (1958).
—, and B. Pansky: The effect of age of both donor and host on the growth of pancreatic homografts in the cheek pouches of normal and diabetic hamsters. Transplant. Bull., 28, 55 (1961).
—, B. Pansky, and M.S. Jacobs: The effect of pancreatic homografts on the diabetic state of alloxan — treated hamsters. Anat. Rec., 140, 341 (1961).
Pansky, B., E.L. House, and M.S. Jacobs: Effect of hormones on pancreatic transplants in both normal and diabetic hamsters. Am. J. Physiol., 203, 487 (1962).
Browning, H., and P. Resnik: Homologous and heterologous transplantation of pancreatic tissue in normal and diabetic mice. J. Biol. Med., 24, 141 (1951–1952).
Coupland, R.E.: Growth of pancreatic islet tissue in the anterior chamber of the eye. Nature, 179, 51 (1957).
Hultquist, G.T., and J. Thorell: Isolation of islet tissue by transplantation. Nord. Med., 69, 47 (1963).
Grimelius, L., G.T., Hultquist, J. Thorell, and L. Winbladh: Studies on islet tissue transplants in the anterior chamber of the eye in rats. In Proceedings of the 3 rd International Symposium, Stockholm (1963). Pergamon Press: the Structure and Metabolism of the Pancreatic Islets, p. 173 (1964).
Sak, M.F., I.A. Macchi, and S.B. Beaser: Structural and functional characteristics of neonatal pancreas homografts in alloxan diabetic golden hamsters. Proceedings of the fifth congress of the International diabetes federation, Toronto p. 74 (1964), Excerpta Medica, Toronto 1964).
Du Bois, A.M., and A.E. Gonet: Régénération des îlots de Langerhans au cours de la correction du diabète expérimental du rat par bréphoplastie pancréatique. Z. Zell. Forsch., 53, 481 (1961).
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Supported by the Fonds National Suisse de la Recherche Scientifique, grant No. 3244 and by a grant in aid from Diabetes Foundation, Incorporated, Boston, Massachusetts.
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Gonet, A.E., Renold, A.E. Homografting of fetal rat pancreas. Diabetologia 1, 91–96 (1965). https://doi.org/10.1007/BF00421481
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DOI: https://doi.org/10.1007/BF00421481