Effects of islet grafts of MHC-compatible donors on glucose metabolism in the spontaneously diabetic BB/Wor rat.

Complete recovery of the diabetic process occurred in spontaneously diabetic BB/Wor rats after the transplantation of islets of MHC-compatible donor rats. Islets were isolated from diabetes-resistant BB/Wor rats and were cultured for 4 days at 37 degrees C. The islets were then hand-picked and each BB/Wor rat with spontaneous diabetes received a total of 10 islets per g of body weight injected either into the immunologically privileged abdominal testis or into the non-immunologically favored renal subcapsular space. No immunosuppression was given to the recipients. After a period of at least 80 days of normoglycemia, the effects of an intravenous glucose injection on serum glucose and insulin levels were assessed. The grafts and the pancreases were then surgically removed and the insulin content of each organ site determined. The results showed that normoglycemia and a rapid weight gain were induced whether the rats were given an intratesticular or a renal, subcapsular islet graft. The amounts of extracted insulin recovered from the grafts after 83-259 days of normoglycemia were not significantly different from the pancreatic insulin content of age-matched control rats. But, despite the survival of a large mass of insulin-producing cells, glucose tolerance was impaired with a blunted insulin response and a delayed return of serum glucose to basal levels. Histologic examination of the islet grafts between 214 and 269 days after transplantation showed remarkable preservation of the islets with no evidence of an inflammatory reaction. Successful transplantation did not, however, lead to a recovery of the native pancreas of the BB/Wor recipient.(ABSTRACT TRUNCATED AT 250 WORDS)