Abstract
Several years ago, techniques have been developed for isolation of pancreatic islets from rodent pancreas1,2 in order to permit in vitro studies on the mechanism and events involved in the formation, storage, and release of insulin by pancreatic B-cells and other hormones produced by the islet cells3. A natural outgrowth of this development was to determine whether transplants of isolated islets into inbred strains of rodents (syngeneic transplantation), with experimentally induced diabetes, would achieve and maintain normoglycaemia in the recipients. Since the pioneering work of Lacy4, who demonstrated the successful reversal of diabetes with syngeneic islet grafts, studies were performed to determine the effect on diabetic complications, as they occur in rodents. The islet transplants prevented or reversed many of the complications caused by hyperglycaemia, thus the possibility was raised to utilize pancreatic islets for transplantation in diabetic patients4–6. In consequence, primary experimental, and later clinical research was concentrated on the development of methods for mass isolation of islets, for immunological procedures, which allowed allogeneic or xenogeneic transplantation without continuous immunosuppression, and for clinical application in diabetic patients. Even, if the ultimate goal of islet transplantation is to cure diabetic patients, the syngeneic islet transplantation can be used to improve our understanding of pancreatic B-cells in normal and abnormal conditions. This review will summarize some results obtained when fetal, neonatal or adult pancreatic islets were grafted into inbred animals.
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References
S. Moskalewski: Isolation and culture of the islets of Langerhans of the guinea pig. Gen&Comp.Endocrinol. 5:342–348(1965).
P.E. Lacy, and M Kostianovsky: A method for the isolation of intact islets of Langerhans from the rat pancreas. Diabetes 16: 35–39 (1967).
H.J. Hahn: Die isolierte Langerhanssche Insel, ein Modell zur Untersuchung der Insulinsekretion in vitro. Endokrinol. 71: 308–329 (1978).
W.F. Ballinger and P.E. Lacy. Transplantation of intact pancreatic islets in rats. Surgery 72: 175–186 (1972).
D.W.R. Gray and P.J. Morris: Developments in isolated pancreatic islet transplantation. Transplantation 43: 321–329(1987).
P.E. Lacy: Studies of islet cell transplantation. Diab. Rev. 1: 75–92 (1993).
H.J. Brömme, H.J. Hahn and W. Blech: Biphasic release of insulin from islets of Langerhans after their transplan-tation into the liver of rats, Horm. Metab. Res. 20: 138–140 (1988).
H.J. Brömme, H.J. Hahn, S. Lucke, W. Hildebrandt and W. Blech: Arginine stimulated insulin and glucagon release from islets transplanted into the liver of diabetic rats. Horm. Metab. Res. 21: 587–589 (1989).
W. Hildebrandt: Thesis, Medical Faculty University Halle (1994).
A. Dunger, C. Kauert, H.J. Brömme, W. Hildebrandt, W. Blech and H.J. Hahn: Functional response of a limited β-cell mass to long-term hypgerglycemia. Pancreas 9: 186–192 (1994).
M.D. Menger, P. Vajkoczy, R. Leiderer, S. Jäger and K. Messmer: Influence of experimental hyperglycemia on microvascular blood perfusion of pancreatic islet isografts. J. Clin. Invest. 90: 1361–1369 (1992).
M.D. Menger, P. Vajkoczy, C. Beger, and K. Messmer: Orientation of micro vascular blood flow in pancreatic islet isografts. J. Clin. Invest. 93: 2280–2285 (1994).
N. Noda, K. Ina, Y. Yasunami, S. Ryu, J. Ono and R. Takaki: Reinnervation of intraportal islet allografts in rats. Transplantation 55: 664–665 (1993).
O. Korsgren, A. Andersson, L. Jansson, and F. Sundler Reinnervation of syngeneic mouse pancreatic islets transplanted into renal subcapsular space. Diabetes 41: 130–135 (1992).
A. Gardemann, K. Jungermann, V. Groβe, L. Cossel, F. Wohlrab, H.J. Hahn, W. Blech and W. Hildebrandt: Intraportal transplantation of pancreatic islets into livers of diabetic rats: Reinnervation of islets and regulation of insulin secretion by the hepatic sympathetic nerves. Diabetes 43: 1345–1352 (1994).
E.T. Shapiro, S. Strasser, and K.S. Polonsky: Persistence of oscillatory insulin secretion in denervated islet cell autografts. Transplantation 52: 574–575 (1991).
D. Heinzmann: Die Wirkung einer einzeitigen Bestrahlung mit 60Co auf Parameter des Glukosestoff-wechsels in vivo und auf Funktionen der isolierten Langerhansschen Insel in vitro. Thesis, Med. Acad. Magdeburg (1987).
B. Kuttler, S. Schmidt, I. Klöting and O. Stark: In vitro and in vivo behaviour of rat islets of Langerhans treated with MHC antisera and complement. Exp. Clin. Endocrinol. 89: 83–88 (1987).
M. Gotoh, T. Kanai, K. Dono, J. Porter, T. Maki and A.P. Monaco: Gamma-irradiation as a tool to reduce immunogenicity of islet allo-and xenografts. Horm.Metab.Res. Suppl. Ser. 25: 89–92 (1990).
J. Mason: Pharmocology of cyclosporine (Sandimmune)-VII. Pathophysiology and toxicology of cyclosporine in humans and animals. Pharmacol. Rev. 42: 423–434 (1989).
R.K. Sibley, D.E.R. Sutherland, F. Goetz, and A.F. Michael: Recurrent diabetes mellitus in the pancreas iso-and allograft. A light and electron microscopic and immunohistochemical analysis of four cases. Lab. Invest. 53: 132–144 (1985).
H.J. Hahn, C. Kauert, A. Dunger, B. Kuttler, and T. Diamantstein: Interleukin 2 receptor targeted immuno-therapy in the prevention of autoimmune beta-cell destruction as observed in diabetic BB/OK rats grafted with BB/OK rat islets. Autoimmunity 5: 139–142 (1989).
H.J. Hahn, S. Lucke, B. Kuttler, A. Dunger, H.D. Volk, and T. Diamantstein: Investigations of diabetes-prone normoglycaemic BB rats. Lessons from animal diabetes 3: 30–33 (1990).
S. Lucke, W. Besch, C. Kauert, and H.J. Hahn: The endocrine pancreas of BB/OK-rats before and at diagnosis of hyperglycaemia. Exp. Clin. Endocrinol. 91: 161–170 (1988).
B. Kuttler, A. Dunger, H.D. Volk, T. Diamantstein and H.J. Hahn: Prevention and suppression of autoimmune pancreatic beta-cell destruction in BB rats by syngeneic lymphocytes obtained from long-term normoglycaemic donors. Diabetologia 34: 74–78 (1991).
B. Kuttler, C. Mathieu, M. Waer, H.J. Hahn, and R. Bouillon: Lack of disease recurrence in diabetic BB/PFD rats after syngeneic islet transplantation. Autoimmunity 15: 107–112 (1993).
H.J. Hahn, J. Gerdes, S. Lucke, L. Liepe, C. Kauert, H.D. Volk, H.H. Wacker, S. Brocke, H. Stein, and T. Diamantstein: Phenotypical characterization of the cells invading pancreatic islets of diabetic BB/OK rats: effect of interleukin 2 receptor-targeted immunotherapy. Eur. J. Immunol. 18: 2037–2042 (1988).
H. Wanka, B. Kuttler, and H.J. Hahn: Is the in vitro destruction of pancreatic islets MHC-dependent? Diabetologia 36: Suppl. 19, A9 (1993).
H.J. Hahn, B. Kuttler, F. Laube, and F. Emmrich: Anti-CD4 therapy in recent-onset IDDM. Diab. Metab. Rev. 9:323–328(1993).
T. Diamantstein, and H.J. Hahn: Interleukin-2 receptor-targeted immune therapy. In: Monoclonal antibodies and peptide therapy in autoimmune diseases. (ed. J.F. Bach) Marcel Dekker, Inc. N.Y., Basel, Hong Kong, pp. 295–318 (1993).
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Hahn, H.J., Kuttler, B. (1997). The Syngeneic Islet Transplantation to Study Physiology and Pathophysiology of Pancreatic β-Cells. In: Soria, B. (eds) Physiology and Pathophysiology of the Islets of Langerhans. Advances in Experimental Medicine and Biology, vol 426. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-1819-2_54
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DOI: https://doi.org/10.1007/978-1-4899-1819-2_54
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