THE AMELIORATION OF HYPERGLYCEMIA IN STREPTOZOTOCIN-INDUCED DIABETIC RATS AFTER THE INTRAPORTAL TRANSPLANTATION OF AN INSUFFICIENT NUMBER OF ISLETS BY NICOTINAMIDE TREATMENT

The purpose of the present study was to determine whether or not hyper glycemia in streptozotocin (STZ)-induced diabetic rats after the intra portal transplantation of an insufficient number of isogenic islets ca n be ameliorated by nicotinamide treatment, WKA/Qdj (RT 1(u)) rats wer e used both as donors and recipients, Islets were isolated by the coll agenase technique, A total of 350 islets was transplanted into the liv er via the portal vein of the STZ-induced diabetic rats, Either nicoti namide (NA, 0.5 g/kg) or a vehicle (saline) was administered ip once a day for 60 days after transplantation, All the diabetic rats without islet transplantation remained hyperglycemic irrespective of the NA tr eatment. All the recipients (n=12) bearing the islet grafts and treate d with saline remained hyperglycemic (>400 mg/dl) at 60 days after tra nsplantation, In marked contrast, all the recipients (n=18) with islet grafts and treated with NA became normoglycemic (<200 mg/dl) at 16.2/-7.1 days (mean +/- SD) after transplantation. Morphologically, islet s were easily found in the liver of the recipients, Aldehyde-fuchsin s tain revealed that the beta cells in the islet grafts of the NA treate d recipients were well granulated, whereas those treated with saline w ere degranulated. The insulin content of the liver bearing the grafts treated with either NA or saline was 116.3+/-26.0 mu g/liver (n=4) or 5.7+/-2.2 mu g (n=4), respectively, while that of 350 donor islets was 29.4+/-2.5 mu g (n=5), The insulin content of the pancreas in the NA- or saline-treated recipients was 27.3+/-10.6 mu g/pancreas (n=4) or 2 .7+/-1.2 mu g (n=4), respectively, while those of the pancreas from th e diabetic rats without transplantation was 1.9+/-0.7 mu g (n=4) or 1. 6+/-0.8 mu g (n=5), respectively, These findings clearly demonstrate t hat the hyperglycemia in the STZ-diabetic recipients after transplanta tion of an insufficient number of islets can be ameliorated while, in addition, the islet mass in the liver as well as the endogenous pancre as both increase in size with nicotinamide treatment,