Implantation site-dependent dysfunction of transplanted pancreatic islets.
OBJECTIVE
Clinical islet transplantations are performed through infusion of islets via the portal vein into the liver. This study aimed at characterizing the influence of the implantation microenvironment on islet graft metabolism and function.


METHODS
Islets were transplanted into their normal environment, i.e., the pancreas, or intraportally into the liver of mice. One month posttransplantation, the transplanted islets were retrieved and investigated for changes in function and gene expression.


RESULTS
Insulin content, glucose-stimulated insulin release, (pro)insulin biosynthesis, and glucose oxidation rate were markedly decreased in islets retrieved from the liver, both when compared with islets transplanted into the pancreas and endogenous islets. Islets transplanted into the pancreas showed normal insulin content, (pro)insulin biosynthesis, and glucose oxidation rate but increased basal insulin secretion and impaired glucose stimulation index. Gene expression data for retrieved islets showed downregulation of pancreatic and duodenal homeobox gene-1, GLUT-2, glucokinase, mitochondrial glycerol-phosphate dehydrogenase, and pyruvate carboxylase, preferentially in intraportally transplanted islets.


CONCLUSIONS
Islets transplanted into their normal microenvironment, i.e., the pancreas, display gene expression changes when compared with endogenous islets but only moderate changes in metabolic functions. In contrast, site-specific properties of the liver markedly impaired the metabolic functions of intraportally transplanted islets.
Lau
Joey
J
Department of Medical Cell Biology, Biomedical Center, Uppsala University, Uppsala, Sweden. joey.lau@mcb.uu.se
Mattsson
Göran
G
Carlsson
Carina
C
Nyqvist
Daniel
D
Köhler
Martin
M
Berggren
Per-Olof
PO
Jansson
Leif
L
Carlsson
Per-Ola
PO
D000818:Animals; D018929:Cell Culture Techniques; D004195:Disease Models, Animal; D017930:Genes, Reporter; D005947:Glucose / Q000494:pharmacology / Q000502:physiology; D007328:Insulin / Q000378:metabolism / Q000502:physiology; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D016381:Islets of Langerhans Transplantation / Q000379:methods / Q000473:pathology*; D008099:Liver; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D016042:Transplantation, Heterotopic
D007328:Insulin; D005947:Glucose