| First Author | Shrivastava V | Year | 2021 |
| Journal | Sci Rep | Volume | 11 |
| Issue | 1 | Pages | 10372 |
| PubMed ID | 33990661 | Mgi Jnum | J:314449 |
| Mgi Id | MGI:6713096 | Doi | 10.1038/s41598-021-89745-9 |
| Citation | Shrivastava V, et al. (2021) Beta cell adaptation to pregnancy requires prolactin action on both beta and non-beta cells. Sci Rep 11(1):10372 |
| abstractText | Pancreatic islets adapt to insulin resistance of pregnancy by up regulating beta-cell mass and increasing insulin secretion. Previously, using a transgenic mouse with global, heterozygous deletion of prolactin receptor (Prlr(+/-)), we found Prlr signaling is important for this adaptation. However, since Prlr is expressed in tissues outside of islets as well as within islets and prolactin signaling affects beta-cell development, to understand beta-cell-specific effect of prolactin signaling in pregnancy, we generated a transgenic mouse with an inducible conditional deletion of Prlr from beta-cells. Here, we found that beta-cell-specific Prlr reduction in adult mice led to elevated blood glucose, lowed beta-cell mass and blunted in vivo glucose-stimulated insulin secretion during pregnancy. When we compared gene expression profile of islets from transgenic mice with global (Prlr(+/-)) versus beta-cell-specific Prlr reduction (betaPrlR(+/-)), we found 95 differentially expressed gene, most of them down regulated in the Prlr(+/-) mice in comparison to the betaPrlR(+/-) mice, and many of these genes regulate apoptosis, synaptic vesicle function and neuronal development. Importantly, we found that islets from pregnant Prlr(+/-) mice are more vulnerable to glucolipotoxicity-induced apoptosis than islets from pregnant betaPrlR(+/-) mice. These observations suggest that down regulation of prolactin action during pregnancy in non-beta-cells secondarily and negatively affect beta-cell gene expression, and increased beta-cell susceptibility to external insults. |
