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Increased numbers of low oxygenated pancreatic islets after intraportal transplantation
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
Manuscript (Other academic)
URN: urn:nbn:se:uu:diva-94773OAI: oai:DiVA.org:uu-94773DiVA: diva2:168748
Available from: 2006-09-08 Created: 2006-09-08 Last updated: 2010-01-13Bibliographically approved
In thesis
1. The Microvasculature of Endogenous and Transplanted Pancreatic Islets: Blood Perfusion, Oxygenation and Islet Endocrine Function
Open this publication in new window or tab >>The Microvasculature of Endogenous and Transplanted Pancreatic Islets: Blood Perfusion, Oxygenation and Islet Endocrine Function
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Type 1 diabetes mellitus affects millions of people worldwide. Islet transplantation is a minimal invasive surgical procedure that restores euglycemia and halts the progression of diabetic complications. However, despite transplantation of islets from multiple donors most patients reverse to hyperglycemia within five years. New strategies to improve long-term outcome of islet transplantation are indispensable. This thesis studied differences in the microvasculature between endogenous and transplanted pancreatic islets, and investigated means to improve islet graft revascularization and function. Islet graft microvessels were similar to endogenous islets responsive to adenosine, angiotensin II and nitric oxide (NO). Recipient hyperglycemia induced a higher basal islet graft blood flow, which also was less dependent on NO than in normoglycemic recipients. Transplantation of freshly isolated instead of cultured islets improved graft revascularization, oxygenation and function. Pretreatment of islets with vascular endothelial growth factor decreased their expression of matrix metalloproteinase-9 (MMP-9) and impaired graft revascularization. Moreover, MMP-9 pretreatment per se improved graft revascularization. In vivo, 20-25% of all endogenous rat islets was low oxygenated (pO2 <10 mmHg). Changes in the islet mass, by means of whole-pancreas transplantation, doubled the fraction of low oxygenated islets in the endogenous pancreas of transplanted animals, whereas this fraction almost completely disappeared after a 60% partial pancreatectomy. Interestingly, oxygenation was related to metabolism, since well oxygenated islets in vivo had 50% higher leucine-dependent protein biosynthesis, which includes (pro)insulin biosynthesis. In intraportally transplanted islets, the low oxygenated fraction of islets was markedly increased one day post-transplantation, and the oxygenation remained low following revascularization. In summary, these data suggest that a better revascularization of transplanted islets can improve graft function. Furthermore, the oxygenation and metabolism of endogenous islets is tightly regulated. This regulation seems to be disturbed following transplantation, which may contribute to long-term islet graft failure.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2006. 83 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 167
Cell biology, diabetes mellitus, pancreatic islets, islet transplantation, vascular engraftment, islet microcirculation, oxygenation, blood flow, protein biosynthesis, Cellbiologi
urn:nbn:se:uu:diva-7107 (URN)91-554-6633-8 (ISBN)
Public defence
2006-09-30, B22, Biomedicum, Husargatan 3, Uppsala, 09:15
Available from: 2006-09-08 Created: 2006-09-08Bibliographically approved

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