IMPROVED OUTCOME OF ISLET TRANSPLANTATION IN INSULIN-TREATED DIABETICMICE - EFFECTS ON BETA-CELL MASS AND FUNCTION

Insulin treatment may improve the outcome of islet transplantation. To determine the effects of insulin treatment on transplanted islets, 4 groups of streptozotocin-diabetic C57BL/6 mice were transplanted with 100 islets, an insufficient beta-cell mass to restore normoglycaemia. Groups 1 (n = 12) and 2 (n = 12), were kept normoglycaemic with insuli n treatment from day 10 before transplantation to day 14 after transpl antation; groups 3 (n = 12) and 4 (n = 18), were not treated with insu lin. Grafts were harvested 14 (groups 1 and 3) or 60 (groups 2 and 4) days after transplantation and beta-cell mass and replication were mea sured. When insulin was discontinued all mice maintained normo-glycaem ial in contrast, non-insulin-treated groups remained hyperglycaemic th roughout the study. Fourteen days after transplantation the beta-cell mass was reduced both in group 1 (0.09 +/- 0.01 mg) and group 3 (0.14 +/- 0.02 mg) compared to the initially transplanted mass (0.22 +/- 0.0 2 mg, p < 0.01); beta-cell replication and area did not change in grou p 1, but were increased in group 3. Insulin content, expressed as a fu nction of beta-cell mass, was maintained in group 1 grafts (12.5 +/- 2 .0 mu g/mg), but was severely reduced in group 3 (1.0 +/- 0.2 mu g/mg) compared to non-transplanted islets (20.4 +/- 3.3 mu m/mg). In group 2, beta-cell mass increased when insulin was discontinued; 60 days aft er transplantation beta-cell mass was similar to the initially transpl anted mass (0.23 +/- 0.04 mg), glucose levels after an intraperitoneal glucose challenge were normal, and insulin content was preserved (19. 6 +/- 2.7 mu g/mg). In contrast, beta-cell mass was progressively redu ced in group 4 (0.08 +/- 0.02 mg, p < 0.001). In summary, insulin trea tment reduced the beta-cell mass needed to achieve normoglycaemia in i slet transplantation. Islets transplanted to insulin-treated mice show ed better beta-cell function, preserved insulin content, and were able to increase their beta-cell mass to meet an increased functional dema nd.