Format

Send to

Choose Destination
Diabetes. 2016 Aug;65(8):2331-41. doi: 10.2337/db15-1527. Epub 2016 May 23.

Gestational Diabetes Mellitus From Inactivation of Prolactin Receptor and MafB in Islet β-Cells.

Author information

1
Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA Division of Endocrinology, Gerontology and Metabolism, Department of Medicine, Stanford University School of Medicine, Stanford, CA.
2
Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN.
3
Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA.
4
Department of Neurobiology, Harvard Medical School, Boston, MA.
5
Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA seungkim@stanford.edu.

Abstract

β-Cell proliferation and expansion during pregnancy are crucial for maintaining euglycemia in response to increased metabolic demands placed on the mother. Prolactin and placental lactogen signal through the prolactin receptor (PRLR) and contribute to adaptive β-cell responses in pregnancy; however, the in vivo requirement for PRLR signaling specifically in maternal β-cell adaptations remains unknown. We generated a floxed allele of Prlr, allowing conditional loss of PRLR in β-cells. In this study, we show that loss of PRLR signaling in β-cells results in gestational diabetes mellitus (GDM), reduced β-cell proliferation, and failure to expand β-cell mass during pregnancy. Targeted PRLR loss in maternal β-cells in vivo impaired expression of the transcription factor Foxm1, both G1/S and G2/M cyclins, tryptophan hydroxylase 1 (Tph1), and islet serotonin production, for which synthesis requires Tph1. This conditional system also revealed that PRLR signaling is required for the transient gestational expression of the transcription factor MafB within a subset of β-cells during pregnancy. MafB deletion in maternal β-cells also produced GDM, with inadequate β-cell expansion accompanied by failure to induce PRLR-dependent target genes regulating β-cell proliferation. These results unveil molecular roles for PRLR signaling in orchestrating the physiologic expansion of maternal β-cells during pregnancy.

PMID:
27217483
PMCID:
PMC4955982
DOI:
10.2337/db15-1527
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center