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.
Movassat
J
J
Laboratory of Physiopathology of Nutrition, Université Paris, France.
Saulnier
C
C
Portha
B
B
D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D001973:Bromodeoxyuridine; D002455:Cell Division / Q000187:drug effects; D005260:Female; D007328:Insulin / Q000008:administration & dosage*; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration / Q000187:drug effects; D013311:Streptozocin / Q000494:pharmacology*
D001786:Blood Glucose; D007328:Insulin; D013311:Streptozocin; D001973:Bromodeoxyuridine