THE EFFECT OF PREEXISTING LONG-TERM DIABETES ON THE OUTCOME AFTER ISLET TRANSPLANTATION IN RATS

Studies of islet transplantation conducted immediately following diabe tes induction may not accurately reflect the clinical situation. Long- term preexisting diabetes with generalized microvasculature complicati on might adversely affect the outcome after islet transplantation. The present study tested this hypothesis by evaluating the effect of long -term preexisting diabetes on glucose-induced insulin secretion up to 6 months after transplantation of two different quantities of islets. One thousand two hundred or 2,400 islets were isotransplanted into the left renal subcapsular space at 10 days (acute diabetes), 3 months (c hronic diabetes), or 6 months (long-term diabetes) after diabetes indu ction by streptozotocin in the rat. In addition, one group of diabetic rats in which normoglycemia was maintained with exogenous insulin tre atment for 6 months was then transplanted with 1,200 islets, Intraveno us glucose tolerance tests were performed at 10, 90, and 180 days afte r islet transplantation. Islet transplantation normalized the basal bl ood glucose levels within 24-48 h in all transplanted groups that rema ined normal for the entire study period of 6 months, with no differenc es among acute, chronic, or long-term diabetes. Basal plasma insulin l evels were also normalized in all transplanted groups, Diabetic (acute , chronic, or long-term) rats transplanted with 2,400 islets achieved normal glucose-induced insulin secretion at 10 and 90 days after trans plantation. In contrast, glucose-induced insulin secretion was impaire d in rats transplanted with only 1,200 islets, with no differences amo ng acute, chronic, and long-term diabetes. However, at 180 days after transplantation, long-term diabetic rats transplanted with 2,400 islet s had impaired insulin secretion compared to normal controls. Insulin- treated long-term diabetic rats transplanted with 1,200 islets had nor mal glucose-induced insulin secretion at 10 days after transplantation , However, at 90 and 180 days after transplantation, insulin-treated l ong-term diabetic rats had impaired glucose-induced insulin secretion which was not different from nontreated transplanted long-term diabeti c rats. It is concluded that long-term preexisting diabetes has no imp act on the early outcome after islet transplantation. However, it may adversely affect the long-term function of the transplanted islets. Al so, transplantation of a sufficient islet mass is the critical factor in achieving complete glucose homeostasis.