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Diabetes 53:948-954, 2004
© 2004 by the American Diabetes Association, Inc.

Evidence of Functional Impairment of Syngeneically Transplanted Mouse Pancreatic Islets Retrieved from the Liver

Göran Mattsson1, Leif Jansson1, Astrid Nordin1, Arne Andersson1, and Per-Ola Carlsson1,2

1 Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden
2 Department of Medical Sciences, Uppsala University, Uppsala, Sweden

A drawback in pancreatic islet transplantation is the large number of islets needed to obtain insulin independence in patients with diabetes. This most likely reflects extensive posttransplantation islet cell death and functional impairment of the remaining endocrine cells. We aimed to develop an experimental method to retrieve transplanted islets from the mouse liver, which would enable comparisons of transplanted and endogenous islets and provide valuable information on functional changes induced by intraportal transplantation. Transplanted islets were obtained by retrograde perfusion of the liver with collagenase. The identity of retrieved tissue as transplanted islets was confirmed by intravital staining, immunohistochemistry, and electron microscopy. The retrieved islets, irrespective of whether they had resided in diabetic or nondiabetic recipients, had a markedly lower insulin content and glucose-stimulated insulin release when compared with isolated endogenous islets. The glucose oxidation rate was also markedly lower in the retrieved islets, suggesting mitochondrial dysfunction. These disturbances in insulin content, insulin release, and glucose oxidation rate were not reversed by a few days of culture after retrieval. The results implicate changes in islet function after intraportal transplantation. Such dysfunction may contribute to the high number of islets needed for successful transplantation in diabetic individuals.


Address correspondence and reprint requests to Göran Mattsson, Department of Medical Cell Biology, Biomedical Center, Husargatan 3, Box 571, Uppsala University, SE-751 23 Uppsala, Sweden. E-mail: goran.mattsson{at}medcellbiol.uu.se


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Copyright © 2004 by the American Diabetes Association.