Abstract
Streptozotocin-induced diabetes in the rat can be reversed by the transplantation of isogenic islets of Langerhans from neonatal donors. We studied the morphology of intraportally transplanted islets with the aid of the immunoperoxidase staining technique to identify insulin-, glucagon-, somatostatin-, and pancreatic polypeptide-containing cells at 24 hours, 48 hours, 1 week, 2 weeks, 4 weeks, 39 weeks, and 65 weeks after transplant. Embolized pancreatic tissue, composed of approximately 80% acini and 20% islets, is initially distributed throughout the liver mainly to terminal branches of the portal system. Endothelialization and organization occur rapidly with the smaller fragments and within the first 4 weeks for larger thrombi. Exocrine pancreatic elements largely disappear as islet cells move into the hepatic lobules from the portal spaces. At 65 weeks after transplant, all islet cell types can be identified within large complex islet structures. The results of this study establish the survival and continued function of all known rat pancreatic islet cell types long after transplantation and support the theory that islet transplantation may represent the most physiologic replacement of hormonal deficiencies in the diabetic recipient.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Erlandsen S. L., Hegre O. D., Parsons J. A., McEvoy R. C., Elde R. P. Pancreatic islet cell hormones distribution of cell types in the islet and evidence for the presence of somatostatin and gastrin within the D cell. J Histochem Cytochem. 1976 Jul;24(7):883–897. doi: 10.1177/24.7.60437. [DOI] [PubMed] [Google Scholar]
- Erlandsen S. L., Parsons J. A., Burke J. P., Redick J. A., Van Orden D. E., Van Orden L. S. A modification of the unlabeled antibody enzyme method using heterologous antisera for the light microscopic and ultrastructural localization of insulin, glucagon and growth hormone. J Histochem Cytochem. 1975 Sep;23(9):666–677. doi: 10.1177/23.9.1176760. [DOI] [PubMed] [Google Scholar]
- Feldman S., Scharp D., Hirshberg G., Dodi G., Ballinger W., Lacy P. Streptozotocin-induced liver tumors. Transplantation. 1977 Aug;24(2):152–154. doi: 10.1097/00007890-197708000-00010. [DOI] [PubMed] [Google Scholar]
- GOMORI G. Aldehyde-fuchsin: a new stain for elastic tissue. Am J Clin Pathol. 1950 Jul;20(7):665–666. [PubMed] [Google Scholar]
- Greider M. H., Rosai J., McGuigan J. E. The human pancreatic islet cells and their tumors. II. Ulcerogenic and diarrheogenic tumors. Cancer. 1974 May;33(5):1423–1443. doi: 10.1002/1097-0142(197405)33:5<1423::aid-cncr2820330529>3.0.co;2-r. [DOI] [PubMed] [Google Scholar]
- Griffith R. C., Scharp D. W., Hartman B. K., Ballinger W. F., Lacy P. E. A morphologic study of intrahepatic portal-vein islet isografts. Diabetes. 1977 Mar;26(3):201–214. doi: 10.2337/diab.26.3.201. [DOI] [PubMed] [Google Scholar]
- Hegre O. D., Leonard R. J., Erlandsen S. L., McEvoy R. C., Parsons J. A., Elde R. P., Lazarow A. Transplantation of islet tissue in the rat. Acta Endocrinol Suppl (Copenh) 1976;205:257–281. [PubMed] [Google Scholar]
- Hegre O. D., Leonard R. J., Schmitt R. V., Lazarow A. Isotransplantation of organ-cultured neonatal pancreas: reversal of alloxan diabetes in the rat. Diabetes. 1976 Mar;25(3):180–189. doi: 10.2337/diab.25.3.180. [DOI] [PubMed] [Google Scholar]
- Kemp C. B., Knight M. J., Scharp D. W., Ballinger W. F., Lacy P. E. Effect of transplantation site on the results of pancreatic islet isografts in diabetic rats. Diabetologia. 1973 Dec;9(6):486–491. doi: 10.1007/BF00461694. [DOI] [PubMed] [Google Scholar]
- Lazarow A., Wells L. J., Carpenter A. M., Hegre O. D., Leonard R. J., McEvoy R. C. The Banting Memorial Lecture 1973: Islet differentiation, organ culture, and transplantation. Diabetes. 1973 Dec;22(12):877–912. doi: 10.2337/diab.22.12.877. [DOI] [PubMed] [Google Scholar]
- Leonard R. J., Lazarow A., Hegre O. D. Pancreatic islet transplantation in the rat. Diabetes. 1973 Jun;22(6):413–428. doi: 10.2337/diab.22.6.413. [DOI] [PubMed] [Google Scholar]
- Leonard R. J., Lazarow A., McEvoy R. C., Hegre O. D. Islet cell transplantation. Kidney Int Suppl. 1974 Oct;(1):169–178. [PubMed] [Google Scholar]
- Lorenz D., Estel S., Gehrandt F., Dorn A., Petermann J., Beckert R. Histologische und immunohistochemische Untersuchungen an transplantierten isolierten Langerhansschen Inseln bei diabetischen Ratten. Acta Histochem. 1977;58(1):85–99. [PubMed] [Google Scholar]
- Matas A. J., Payne W. D., Grotting J. C., Sutherland D. E., Steffes M. W., Hertel B. F., Najarian J. S. Portal versus systemic transplantation of dispersed neonatal pancreas. Transplantation. 1977 Nov;24(5):333–337. doi: 10.1097/00007890-197711000-00004. [DOI] [PubMed] [Google Scholar]
- Matas A. J., Sutherland D. E., Steffes M. W., Najarian J. S. Islet transplantation using neonatal rat pancreata: quantitative studies. J Surg Res. 1976 Mar;20(3):143–147. doi: 10.1016/0022-4804(76)90132-3. [DOI] [PubMed] [Google Scholar]
- Matas A. J., Sutherland D. E., Steffes M. W., Najarian J. S. Minimal collagenase digestion: amelioration of diabetes in the rat with transplantation of one dispersed neonatal pancreas. Transplantation. 1976 Jul;22(1):71–73. [PubMed] [Google Scholar]
- Orci L., Baetens D., Rufener C., Amherdt M., Ravazzola M., Studer P., Malaisse-Lagae F., Unger R. H. Hypertrophy and hyperplasia of somatostatin-containing D-cells in diabetes. Proc Natl Acad Sci U S A. 1976 Apr;73(4):1338–1342. doi: 10.1073/pnas.73.4.1338. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Orci L., Unger R. H. Functional subdivision of islets of Langerhans and possible role of D cells. Lancet. 1975 Dec 20;2(7947):1243–1244. doi: 10.1016/s0140-6736(75)92078-4. [DOI] [PubMed] [Google Scholar]
- Pipeleers-Marichal M. A., Pipeleers D. G., Cutler J., Lacy P. E., Kipnis D. M. Metabolic and morphologic studies in intraportal-islet-transplanted rats. Diabetes. 1976 Nov;25(11):1041–1051. doi: 10.2337/diab.25.11.1041. [DOI] [PubMed] [Google Scholar]
- Sternberger L. A., Hardy P. H., Jr, Cuculis J. J., Meyer H. G. The unlabeled antibody enzyme method of immunohistochemistry: preparation and properties of soluble antigen-antibody complex (horseradish peroxidase-antihorseradish peroxidase) and its use in identification of spirochetes. J Histochem Cytochem. 1970 May;18(5):315–333. doi: 10.1177/18.5.315. [DOI] [PubMed] [Google Scholar]