Insulin Administration Enhances Growth of the β-Cell Mass in Streptozotocin-Treated Newborn Rats

We have previously reported that the damage caused by streptozotocin (STZ) administration to the β-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 β-cell mass on day 4 to only 10% of the normal value and that after sucb damage, 27% of the corresponding normal β-cell mass was spontaneously regained on day 7. During days 4–7, the contribution of the predicted β-cell growth (due to the replication of preexisting differentiated β-cells) to the total β-cell growth represented only 56%. Therefore, recruitment of new β-cells from a precursor pool indeed represents a significant mechanism for β-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 β-cell damage after STZ administration (total β-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 β-cell regeneration, since on day 7 total β-cell mass was 44% of the corresponding normal β-cell mass. During days 4-7, the contribution of the predicted β-cell growth to the total β-cell growth represented only 32% in the insulin-treated STZ group. Finally the insulin-favored regeneration of the β-cells reflects both an increased replication from differentiated β-cells and an increased neogenesis from precursor/stem cells, with this last pathway being preferentially activated.