Implantation site-dependent dysfunction of transplanted pancreatic islets

Joey Lau, Göran Mattsson, Carina Carlsson, Daniel Nyqvist, Martin Köhler, Per Olof Berggren, Leif Jansson, Per Ola Carlsson

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

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. RESEARCH DESIGN AND 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.

Original languageEnglish (US)
Pages (from-to)1544-1550
Number of pages7
JournalDiabetes
Volume56
Issue number6
DOIs
StatePublished - Jun 1 2007

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Fingerprint Dive into the research topics of 'Implantation site-dependent dysfunction of transplanted pancreatic islets'. Together they form a unique fingerprint.

Cite this