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Evidence of functional impairment of syngeneically transplanted mouse pancreatic islets retrieved from the liver
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
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Article in journal (Refereed) Submitted
URN: urn:nbn:se:uu:diva-90873OAI: oai:DiVA.org:uu-90873DiVA: diva2:163379
Available from: 2003-10-01 Created: 2003-10-01Bibliographically approved
In thesis
1. Experimental Studies on the Vasculature of Endogenous and Transplanted Islets of Langerhans
Open this publication in new window or tab >>Experimental Studies on the Vasculature of Endogenous and Transplanted Islets of Langerhans
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The blood vessels of the pancreatic islets are of crucial importance for oxygen and metabolite supply as well as dispersal of secreted hormones. In addition to this, endothelial cells have an important role in the revascularization process after islet transplantation. Previous studies have reported signs of poor engraftment of transplanted islets, presumably due to impaired revascularization. The aims of this thesis were to investigate the revascularization process of transplanted islets and to examine the role of islet endothelial cells. In this context, the lectin Bandeiraea simplicifolia was found to stain endothelium of both endogenous and transplanted pancreatic islets. By using this lectin we investigated the vascular density of both endogenous and islets transplanted syngeneically beneath the renal capsule, into the spleen or intraportally into the liver of normoglycemic C57BL/6 mice. One month post-transplantation, a time point when the grafts are assumed to be completely revascularized, the vascular density was decreased at all three implantation sites when compared to endogenous islets. Furthermore, most of the blood vessels were located in the graft connective tissue stroma. Similar results were obtained when islet transplant vascular density was determined six months post-transplantation and in cured diabetic animals after one month. In order to evaluate the function of intraportally transplanted islets, we developed a method to retrieve such islets. We treated the implantation organ (liver) first enzymatically (collagenase) and then mechanically, thereafter we could re-isolate the transplanted islets for further in vitro studies. The retrieved islets had a decreased insulin relase, insulin content and glucose oxidation rate when compared to non-transplanted control islets. To understand the role of islet endothelium in the revascularization of transplanted islets we performed angiogenesis GEArray studies on islet endothelial cells, from non-cultured, cultured and transplanted islets. We found that the islet endothelium expressed mRNA for both inhibitors and inducers of angiogenesis, and that this expression differed with time. The functional consequences of this remain to be determined. In summary, the results presented above provide a useful platform for future studies of the morphology and function of islet endothelial cells, especially with a view for elucidating changes induced by islet transplantation.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2003. 34 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1290
Medicine, islets of Langerhans, endothelial cells, islet transplantation, vascular density, diabetes mellitus, Medicin
National Category
Dermatology and Venereal Diseases
urn:nbn:se:uu:diva-3596 (URN)91-554-5749-5 (ISBN)
Public defence
2003-10-25, B21, Biomedicinskt centrum BMC, Uppsala, 10:15
Available from: 2003-10-01 Created: 2003-10-01Bibliographically approved

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