Insulin-induced normoglycemia has shown to have a beneficial effect on the
outcome of pancreatic islets transplanted to diabetic recipients. The aim o
f the study was to identify the insulin treatment that can maximize its ben
eficial effect on islet transplants. Six groups of streptozotocin diabetic
C57B1/6 mice were transplanted (Tx) with 100 syngeneic islets, an insuffici
ent beta cell mass to restore normoglycemia, and were treated with insulin
as follows: group 1 (n = 9). from day 10 before Tx to day 14 after Tx; grou
p 2 (n = 11): from day 6 before Tx to Tx day; group 3 (n = 11): from Tx day
to day 6 after Tx; group 4 (n = 7). from Tx day to day 14 after Tx; group
5 (n = 8): from day 10 to day 24 after Tx; group 6 (n = 18). Tx mice were n
ot treated with insulin. Sixty days after Tx, normoglycemia was achieved in
100% of mice in groups 1, 4, and 5, in 73% of mice in group 2, and in only
45% and 33% of mice in groups 3 and 6, respectively (p < 0.01). Intraperit
oneal glucose tolerance, determined only in normoglycemic mice, was similar
in groups 1, 2, 4, and normal controls. In contrast, normoglycemic mice fr
om groups 3, 5, and 6, exposed to more severe and prolonged hyperglycemia a
fter Tx, showed higher glucose values after glucose injection, suggesting t
hat hyperglycemia had a long-lasting deleterious effect on transplanted bet
a cell function. The initially transplanted beta cell mass was maintained i
n the grafts of normoglycemic mice, but was severely reduced in hyperglycem
ic mice. Transplanted beta cell mass was similar in normoglycemic groups wi
th normal or impaired glucose tolerance, indicating that impaired glucose t
olerance was not due to reduced beta cell mass. In summary, the beneficial
effect of insulin-induced normoglycemia on transplanted islets was maximal
when insulin treatment was maintained the initial 14 days after transplanta
tion. Exposure to sustained hyperglycemia initially after transplantation h
ad a long lasting deleterious effect on transplanted islets.