Normalization of pancreatic exocrine enzymes by islet transplantation in diabetic rats

Abstract

In an effort to evaluate the effectiveness of islet transplantation in correcting exocrine dysfunction, young male Lewis rats were made diabetic by i.v. streptozotocin injection. Diabetes status was confirmed by decrease in insulin and increase in blood glucose and glycosylated hemoglobin levels. Pancreatic islets were isolated from age-matched control syngeneic rats by collagenase digestion followed by purification through a Ficoll gradient. Islets (~1200) were grafted to the liver by intraportal injection to animals at 8 weeks after diabetes was established. Transplanted rats were sacrificed 4 weeks after correction of hyperglycemia. Diabetes resulted in decrease in body weight. Transplantation reversed the body weight loss and led to a body weight gain. Diabetes resulted in a decrease in pancreatic amylase (1.4 ± 0.4 U/mg protein compared with a control value of 121.9 ± 3.2 U/mg protein) and a slight increase in lipase (87.3 ± 5.5 U/mg protein compared with a control value of 69 ± 4.7 U/mg protein). Transplantation completely normalized amylase (132.2 ± 25.0 U/mg protein) and lipase (56.3 ± 3.9 U/mg protein) in spite of an imperfect correction of blood insulin, glucose, and glycosylated haemoglobin levels in these rats. These data demonstrated that islet transplantation is very effective in correcting the exocrine enzyme changes resulting from diabetes. Evaluation of steady-state levels of amylase mRNA in these groups of animals by Northern blots showed a decrease in the amylase mRNA level in diabetes and a return to that of control in transplanted rats, indicating that the control of amylase expression is most likely at the pretranslational level.Key words: islet transplantation, exocrine enzymes, mRNA.