Prophylactic insulin treatment of syngeneically transplanted pre-diabetic BB-DP rats

Type 1 Diabetes Mellitus is characterized by selective destruction of the pancreatic beta-cells in the islets of Langerhans and insulitis. Subcutaneous insulin injections given to diabetes prone BioBreeding (BB-DP) rats reduce diabetes incidence. The underlying mechanism(s) are not known in detail. Previously, we showed that transplantation of 200 syngeneic neonatal islets under the kidney capsule is useful for studying molecular events during diabetes development in BB-DP rats. In the present study we tested if prophylactic insulin treatment of syngeneically transplanted BB-DP rats would protect both islets in situ and transplanted islets from destruction.

BB-DP rats received transplants of 200 syngeneic neonatal islets under the kidney capsule at 30 days of age. They were given a subcutaneous insulin or placebo implant and were compared to control rats. Blood glucose was measured three times weekly. In total, 193 rats were transplanted and rats were sacrificed 7, 23, 50, 90 days post-transplantation or at onset of diabetes. Pancreatic and transplant sections were stained for insulin and mononuclear cell infiltration and insulitis was graded.

Eight (19%) rats developed diabetes in the insulin-treated group and 19 (63%) and 19 (65%) rats in the control and placebo, respectively (p = 0.0002 and p = 0.0001). Onset of diabetes in the insulin treated group was delayed compared to control and placebo, (102, 77 and 81 days of age, respectively (p = 0.0001 and p = 0.0001)). Insulin treatment diminished mononuclear cell infiltration in the islets at day 50 after transplantation compared to placebo. Infiltration pattern in islets in situ correlates with infiltration in transplants (r is 0.9076 and p < 0.001).

These results suggest that insulin-treatment of syngeneically transplanted BB-DP rats considerably decreases the incidence of diabetes and that this model is well suited for studying molecular changes in the islet transplants.