REPEATED INTRAPORTAL INJECTIONS OF SUBTHERAPEUTIC ISLET-CELL ISOGRAFTS RESTORE NORMOGLYCEMIA IN STREPTOZOTOCIN-DIABETIC RATS

Poor engraftment and consequent loss of beta-cell mass could be one of the factors that are responsible for function loss after intraportal islet transplantation (Tx), Streptozotocin-diabetic rats mere transpla nted with syngeneic islets, which were injected into the portal vein v ia an indwelling catheter connected to a subcutaneous port, In Group I (n = 6), 1,000 islets mere injected in a single dose into the liver, In Group II (n = 6), five doses of 200 islets were repeatedly injected over a period of 14 days, for a total of 1,000 islets, In Group III ( n = 4), five decreasing doses of islets were injected over a period of 14 days, for a total of 750 islets. Nonfasting blood glucose (n-FBG) and body weight (b.wt.) were determined twice a meek and an intravenou s glucose tolerance test (IVGTT) was performed at 30 and 90 days. In G roup I, n-FBG decreased in 2 wk from the time of first islet injection , averaging 110 +/- 21.9 mg/dL at 1 mo (p < 0.05 vs. normal controls); this value was maintained throughout the 3-mo duration of the study, In Group II, n-FBG was normalized in 2 wk averaging 90.2 +/- 25 mg/dL on day 12 (p = NS vs, normal: controls) and 75.8 +/- 14.6 mg/dL at 1 m onth (p = NS vs. normal controls); this value was maintained throughou t the 3-mo duration of the study, In Group III, n-FBG decreased to nor mal values in 2 wk, averaging 77 +/- 15.7 mg/dL at 1 mo (p = NS vs. no rmal controls), but normoglycemia was maintained for 40 days and then followed by a progressive increase, Only in Group II, K-G (percent/min decline in glucose level) was not significantly different from that o f normal controls (1.702 +/- 0.531 at 1 mo and 1.676 +/- 0.891 at 3 mo ), while it was significantly lower than normal controls in both Group I and III animals, Body weight increase after Tx correlated with the number of transplanted islets and at 90 days, Group III rats showed le ss increase than Groups I and II (p < 0.05), while no significant diff erences in b.wt. were recorded between Group I and II. The findings in dicate that intraportal islet Tx, injected repeatedly and in small dos es, produced better metabolic effects than injection of the same total number of islets in a single dose. Copyright (C) 1997 Elsevier Scienc e Inc.