β-Cell Growth and Mass Are Preserved in Long-Term Syngeneic Islet Transplantation in Streptozocin-Induced Diabetic Lewis Rats

We determined β-cell replication and mass in basal and stimulated conditions in long-term transplanted islets. Three groups of streptozocin-induced diabetic Lewis rats were transplanted with 1,000 islets (500 islets under left and right kidney capsules). At 2 (Tx-2), 5 (Tx-5), or 9 (Tx-9) months after transplantation, one of the two grafts (basal) was harvested; 14 days later, the contralateral graft (stimulated) was also harvested. Normoglycemia was achieved and maintained in all transplanted rats, although the capacity to respond to a glucose challenge deteriorated slightly 9 months after transplantation. β-cell replication remained stable in Tx-2, Tx-5, and Tx-9 basal grafts and was similar to replication in a control group of nontransplanted rats (0.28 ± 0.06%); replication increased in Tx-2 (0.90 ± 0.23%, P < 0.05) and Tx-9 (0.72 ± 0.09%, P < 0.05) stimulated grafts. β-cell mass in basal grafts was similar to the initially transplanted mass (1.24 ± 0.06 mg) and increased in stimulated grafts in Tx-2 (1.91 ± 0.38 mg, P < 0.05) and Tx-5 (1.73 ± 0.27 mg, P = 0.01) groups, compared with basal grafts, and in Tx-2 and Tx-9 groups (1.92 ± 0.30 mg, P < 0.05), compared with initially transplanted mass. Therefore, β-cell replication and mass were preserved up to 9 months after syngeneic transplantation, and β-cells maintained the capacity to respond to increased metabolic demand, suggesting that replication is not a limiting factor in the survival of transplanted islets.