Abstract
It is well established that the maternal β-cell mass increases during pregnancy in
both humans and rodents to compensate insulin resistance and increased metabolic demand,
and rapidly returns to normal levels post-partum. However, the mechanisms underlying
this adaptation are not well understood. It is established that this process is driven
partly by placental signals, but the contribution of non-placental signals is still
unclear. This study aimed to differentiate between the role of placental and non-placental
signals in regulating the β-cell mass and glucose homeostasis during and after pregnancy.
Pseudopregnant, pregnant and lactating mice were used to study the effects of maternal
hormones on β-cell function during early pregnancy, mid-to-late pregnancy and post-partum,
respectively. Pseudopregnant mice, with circulating hormone levels mirroring those
during pregnancy but lacking placental signals, had significantly increased β-cell
proliferation compared to non-pregnant controls but no change in glucose homeostasis,
suggesting a role for non-placental hormones in increasing β-cell mass. The rate of
β-cell proliferation rate dropped immediately after parturition, but lactating mice
still had a significantly higher rate of β-cell proliferation compared to non-lactating
post-partum mice, suggesting that lactation-related hormones play a role in the controlled
involution of β-cell mass post-partum. These results implicate a role for both non-placental
and placental signals in regulating β-cell mass during and after pregnancy.
Key words
β-cell - pregnancy - diabetes
