BETA-CELL GROWTH AND MASS ARE PRESERVED IN LONG-TERM SYNGENEIC ISLET TRANSPLANTATION IN STREPTOZOCIN-INDUCED DIABETIC LEWIS RATS

We determined beta-cell replication and mass in basal and stimulated c onditions in long-term transplanted islets. Three groups of streptozoc in-induced diabetic Lewis rats were transplanted with 1,000 islets (50 0 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 (basa l) was harvested; 14 days later, the contralateral graft (stimulated) was also harvested. Normoglycemia was achieved and maintained in all t ransplanted rats, although the capacity to respond to a glucose challe nge deteriorated slightly 9 months after transplantation. beta-cell re plication 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. beta-cell mas s 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 +/- 0.3 8 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, beta-cel l replication and mass were preserved up to 9 months after syngeneic t ransplantation, and beta-cells maintained the capacity to respond to i ncreased metabolic demand, suggesting that replication is not a limiti ng factor in the survival of transplanted islets.