Insulin administration enhances growth of the beta-cell mass in streptozotocin-treated newborn rats.

We have previously reported that the damage caused by streptozotocin (STZ) administration to the beta-cells in newborn rats was followed by spontaneous recovery from neonatal diabetes. Our present data indicate that STZ administration on the day of birth (day 1) reduced the total beta-cell mass on day 4 to only 10% of the normal value and that after such damage, 27% of the corresponding normal beta-cell mass was spontaneously regained on day 7. During days 4-7, the contribution of the predicted beta-cell growth (due to the replication of preexisting differentiated beta-cells) to the total beta-cell growth represented only 56%. Therefore, recruitment of new beta-cells from a precursor pool indeed represents a significant mechanism for beta-cell regeneration after STZ during this period of life. Here, we report for the first time that 1) insulin therapy from days 2 to 4 did not significantly influence the occurrence of beta-cell damage after STZ administration (total beta-cell mass on day 4 was reduced to 12% of the normal value) and 2) insulin therapy from days 2 to 6 did improve the otherwise spontaneous beta-cell regeneration, since on day 7 total beta-cell mass was 44% of the corresponding normal beta-cell mass. During days 4-7, the contribution of the predicted beta-cell growth to the total beta-cell growth represented only 32% in the insulin-treated STZ group. Finally the insulin-favored regeneration of the beta-cells reflects both an increased replication from differentiated beta-cells and an increased neogenesis from precursor/stem cells, with this last pathway being preferentially activated.