Long-term function of duct-ligated and free-duct whole pancreas transplants

Abstract

This report compares endocrine and exocrine responses of “free-duct” and “duct-ligated” whole pancreas isografts in Lewis diabetic rats during a 1-year period of observation. Fasting blood sugar, serum amylase, serum insulin, pancreozymin-secretin test, and l-arginine tolerance test assays were performed prior to and at periodic intervals after transplantation. Histological examinations of transplanted and native pancreas were performed monthly on animals in each group. Whole pancreas transplantations led to immediate and sustained normalization of FBS and insulin levels. In the “duct-ligated” group there was a gradual but insignificant decrease of serum insulin levels after 9 months. Depressed serum amylase levels in diabetic rats were reversed in both groups. Isolated islet iso- and allografts also reversed depressed amylase levels. The results of pancreozymin-secretin tests in islet isografted animals supported the postulated trophic effect of endocrine pancreas on exocrine pancreas. Although both whole-pancreas transplant groups showed a normal response to GTT for 12 months after transplantation, the “duct-ligated” group showed a significantly lower response to l-arginine tolerance test than the “free duct” model as early as 4 months after transplantation, suggesting a defect in B-cell function in long-term “duct-ligated” graft. Serial histological examinations of transplanted pancreases revealed more rapid atrophy and more intense fibrosis of acinar tissue in the “duct-ligated” group than in the “free duct” group. These results suggest that a “free duct” pancreatic isograft maintains a more stable endocrine function in a long-term study than does the “duct-ligated” pancreas, and that exocrine dysfunction in diabetic rats may be related to the endocrine disorder which can be reversed by both islet cell and whole-organ pancreatic transplantation.