Recovery of Pancreatic Cells in Response to Long-term Normoglycemia After Pancreas or Islet Transplantation in Severely Streptozotocin Diabetic Adult Rats

In the well-established, high-dose streptozotocin diabetic rat model, it is unknown whether normoglycemia after pancreas or islet transplantation may induce the expression of the glucose recognition structures and stimulate the replication of the few surviving pancreatic cells. Therefore, the endocrine pancreatic tissue was examined immunocytochemically in streptozotocin-treated major histocompatibility complex congenic Lewis rats at 10 and 100 days after transplantation of whole pancreata or isolated islets implanted under the kidney capsule. In the diabetic state the pancreatic cells displayed a weak immunostaining for insulin and glucokinase together with a lack of GLUT2 glucose transporter immunoreactivity in the plasma membrane. Ten days after transplantation, the surviving cells had regained their normal immunostaining for insulin and for the glucose recognition structures glucokinase and the GLUT2 glucose transporter. One hundred days after transplantation, both of whole pancreas or isolated islets, the number of surviving cells in islets of the pancreata of the recipient animals had increased by two-to threefold. The regenerated cells were surrounded by a rim of other endocrine cells. The increase in the number of cells was not accompanied by signs of neogenesis from ductal structures in the pancreata. The authors' observations support the concept that strict long-term maintenance of normoglycemia through adequate supply of insulin from endocrine grafts is the ideal prerequisite for -cell recovery and restitution of the glucose recognition structures, as well as replication of cells in pancreata with end-stage diabetic -cell destruction after high-dose streptozotocin treatment.