The Endothelial Cells in Islets of Langerhans

Abstract

The blood vessels of the pancreatic islets are of crucial importance for oxygen and metabolite supply, and dispersal of secreted hormones. In addition to this, endothelial cells have an important role in the revascularization process after islet transplantation. Studies have reported signs of poor engraftment of transplanted islets, presumably due to impaired revascularization. The aims of this study were to investigate islet endothelial cells and the revascularization process of transplanted islets. The lectin Bandeiraea simplicifolia was found to consistently stain endothelium of both endogenous and transplanted pancreatic islets. By using this marker, we investigated the vascular density of both endogenous and transplanted islets of C57BL/6 mice. One month post-transplantation, a time point when the implants are assumed to be completely revascularized, the graft vascular density was decreased at all investigated 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 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. Enzymatic and mechanic treatment of the liver enabled us to re-isolate the transplanted islets for further in vitro studies. These islets had decreased insulin release, 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 microarray 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. In conclusion, these results provide a useful platform for further studies on the islet endothelium.