Insulin and GLUT2 glucose transporter immunoreactivity in B-cells of whole pancreas isografts and allografts in the streptozotocin-diabetic rat.

The preservation of pancreatic B-cells is essential to ensure normal endocrine function of whole pancreas transplants. At present, however, it is unknown whether or not pancreatic B-cells in allografts display intercellular variations in insulin immunoreactivity and ultrastructure. It is also not clear whether the GLUT2 glucose transporter immunoreactivity is maintained in the plasma membrane after transplantation, as in B-cells under normal conditions. Therefore, pancreatic tissue of isografts and allografts, with or without signs of chronic rejection, was examined in streptozotocin-diabetic rats 10 to 100 days after transplantation by means of immunocytochemistry and electron microscopy. In isografts with preserved exocrine secretion pancreatic B-cells of larger islets exhibited normal heterogeneities in insulin immunoreactivity and in the number of secretory granules, whereas in isografts with suppressed exocrine secretion the heterogeneity was altered or abolished depending on the stage of islet dissociation. Differences in insulin immunoreactivity and ultrastructure were also observed in B-cells of tolerated allografts or those with signs of chronic rejection. In contrast to the localization of the GLUT2 glucose transporter under physiological conditions, GLUT2 glucose transporter immunoreactivity was not restricted to the pancreatic B-cell membrane but was also detected in the cytoplasm after transplantation. The cytoplasmic GLUT2 glucose-transporter localization developed in a time-dependent manner. It was evident 10 days after transplantation in isografts and was detectable still 100 days after transplantation in tolerated as well as in chronically rejected allografts. Interestingly, B-cells in the allografts with a dense insulin immunoreactivity exhibited GLUT2 glucose transporter expression in both localizations, whereas B-cells with a faint insulin immunoreactivity exhibited GLUT2 glucose transporter only in the plasma membrane. This may indicate a relation between the functional state of the pancreatic B-cells and the distribution of the GLUT2 glucose transporter in the cell. The heterogeneity between B-cells in pancreatic isografts and allografts implicates differences in the functional state of the B-cells with respect to insulin storage and release.