gms | German Medical Science

127. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

20.04. - 23.04.2010, Berlin

Betazellregeneration transplantierter Inseln im Mausmodell

Meeting Abstract

  • Christian Krautz - Uniklinikum Dresden, Viszeral-, Thorax- und Gefäßchirurgie, Dresden, Deutschland
  • Steffen Wolk - Uniklinikum Dresden, Viszeral-, Thorax- und Gefäßchirurgie, Dresden, Deutschland
  • Anja Steffen - Paul Langerhans Institut Dresden, Molekulare Diabetologie, Dresden, Deutschland
  • Klaus-Peter Knoch - Paul Langerhans Institut Dresden, Molekulare Diabetologie, Dresden, Deutschland
  • Hans-Detlev Saeger - Universitätsklinikum Carl Gustav Carus der TU Dresden, Klinik und Poliklinik für Viszeral-, Thorax- und Gefäßchirurgie, Dresden, Deutschland
  • Michele Solimena - Universitätsklinikum Dresden, Experimentelle Diabetologie, Dresden, Deutschland
  • Stephan Kersting - Universitätsklinikum Dresden, Klinik und Poliklinik für Viszeral-, Thorax- und Gefäßchirurgie, Dresden, Deutschland

Deutsche Gesellschaft für Chirurgie. 127. Kongress der Deutschen Gesellschaft für Chirurgie. Berlin, 20.-23.04.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. Doc10dgch348

DOI: 10.3205/10dgch348, URN: urn:nbn:de:0183-10dgch3487

Veröffentlicht: 17. Mai 2010

© 2010 Krautz et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Introduction: Antiproliferative effects of immunosuppressants used in human islet transplantation interfere with the capability of the beta cells to balance cell renewal and cell loss. Consequently, long-term use of these drugs might contribute to graft dysfunction in islet transplant recipients. New immunosuppressive regimens are required to improve outcomes.

Materials and methods: Syngeneic islets (300 IEQ) were injected into the right liver lobes of C57BL/6 diabetic mice. Osmotic pumps filled with Bromodeoxyuridine (group 1), Bromodeoxyuridine and Tacrolimus (group 2) or Bromodeoxyuridine and Everolimus (group 3) were implanted. Hepatectomy was performed after 4 weeks. Proliferation of beta cells was detected by BrdU incorporation.

Results: In all transplanted animals normoglycemia was restored. Glucose tolerance was significantly improved after 4 weeks in group 1 (90min: P< 0.012; 120min: P<0.045). This effect was not as strong when animals were treated with Tacrolimus. In contrast, mice that recieved Everolimus showed an impaired glucose tolerance. After 4 weeks 36.3% of all beta cells in group 1 underwent at least on cycle of proliferation. In comparison, beta cells of group 2 had a significantly decreased proliferation rate (21.19%), whereas beta cell proliferation in group 3 (38.36%) remained unchanged.

Conclusion: Beta cells of transplanted islets have a strong capability of self renewal when not affected by immunosuppression or immune assault. In this setting maintenance of glucose homeosstasis improves over time indicating an increase in beta cell mass. Exposure to Tacrolimus clearly inhibits beta cells replication. In contrast, Everolimus does not seem to affect beta cell proliferation, although having a negative impact on glucose tolerance. The use of Everolimus might lead to better long-term results in islet transplantation, due to the lacking inhibition of beta cell proliferation.