| First Author | Toselli C | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 6 | Pages | e100398 |
| PubMed ID | 24940737 | Mgi Jnum | J:244123 |
| Mgi Id | MGI:5912902 | Doi | 10.1371/journal.pone.0100398 |
| Citation | Toselli C, et al. (2014) Contribution of a non-beta-cell source to beta-cell mass during pregnancy. PLoS One 9(6):e100398 |
| abstractText | beta-cell mass in the pancreas increases significantly during pregnancy as an adaptation to maternal insulin resistance. Lineage tracing studies in rodents have presented conflicting evidence on the role of cell duplication in the formation of new beta-cells during gestation, while recent human data suggest that new islets are a major contributor to increased beta-cell mass in pregnancy. Here, we aim to: 1) determine whether a non-beta-cell source contributes to the appearance of new beta-cells during pregnancy and 2) investigate whether recapitulation of the embryonic developmental pathway involving high expression of neurogenin 3 (Ngn3) plays a role in the up-regulation of beta-cell mass during pregnancy. Using a mouse beta-cell lineage-tracing model, which labels insulin-producing beta-cells with red fluorescent protein (RFP), we found that the percentage of labeled beta-cells dropped from 97% prior to pregnancy to 87% at mid-pregnancy. This suggests contribution of a non-beta-cell source to the increase in total beta-cell numbers during pregnancy. In addition, we observed a population of hormone-negative, Ngn3-positive cells in islets of both non-pregnant and pregnant mice, and this population dropped from 12% of all islets cells in the non-pregnant mice to 5% by day 8 of pregnancy. Concomitantly, a decrease in expression of Ngn3 and changes in its upstream regulatory network (Sox9 and Hes-1) as well as downstream targets (NeuroD, Nkx2.2, Rfx6 and IA1) were also observed during pregnancy. Our results show that duplication of pre-existing beta-cells is not the sole source of new beta-cells during pregnancy and that Ngn3 may be involved in this process. |
