Metabolic strategies to predict and improve intrahepatic islet graft function

Abstract

The success rate of intraportal islet grafts and the length of graft survival have been low and variable in diabetic humans. Goal of this work was to outline the principal strategies to predict and improve islet graft. The study of 15 insulin dependent diabetic patients after islet and kidney transplantation allowed us to build a metabolic database. The patients received an hyperglycemic clamp to assess insulin secretion and a euglycemic clamp in combination with tracers of glucose, amino acid and lipid metabolism andindirect calorimetry to assess insulin action. The results of this initial study were used to design new metabolic strategies to predict and improve islet graft function. Special emphasis is given to the importance of developing and studying the metabolic phenotype of transgenic animals with the knock out or the overexpression of genes involved in specific metabolic pathways.