Evidence of functional impairment of syngeneically transplanted mouse pancreatic islets retrieved from the liver.
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.
Mattsson
Göran
G
Department of Medical Cell Biology, Biomedical Center, Uppsala University, Uppsala, Sweden. goran.mattsson@medcellbio.uu.se
Jansson
Leif
L
Nordin
Astrid
A
Andersson
Arne
A
Carlsson
Per-Ola
PO
D000818:Animals; D002469:Cell Separation; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000601:surgery*; D004195:Disease Models, Animal; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D016381:Islets of Langerhans Transplantation / Q000379:methods / Q000473:pathology*; D008099:Liver / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010477:Perfusion; D013806:Theophylline / Q000494:pharmacology; D020858:Tissue and Organ Harvesting / Q000379:methods*; D014185:Transplantation, Isogeneic
D007328:Insulin; D013806:Theophylline; D005947:Glucose