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 afte r such damage, 27% of the corresponding normal beta-cell mass was spon taneously regained on day 7, During days 4-7, the contribution of the predicted beta-cell growth (due to the replication of preexisting diff erentiated beta-cells) to the total beta-cell growth represented only 56%, Therefore, recruitment of new beta-cells from a precursor pool in deed represents a significant mechanism for beta-cell regeneration aft er 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 influen ce the occurrence of S-cell damage after STZ administration (total bet a-cell mass on day 4 was reduced to 12% of the normal value) and 2) in sulin therapy from days 2 to 6 did improve the otherwise spontaneous b eta-cell regeneration, since on day 7 total beta-cell mass was 44% of the corresponding normal beta-cell mass, During days 4-7, the contribu tion of the predicted beta-cell growth to the total beta-cell growth r epresented only 32% in the insulin-treated STZ group. Finally the insu lin-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 preferentiall y activated.