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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Aug 25, 2020 |
| Title |
Regulation of islet function and gene expression by prolactin during pregnancy |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Pancreatic islets adapt to insulin resistance of pregnancy by up regulating beta-cell proliferation and increase insulin secretion. Previously, we found that prolactin receptor (Prlr) signaling is important for this process, as heterozygous prolactin receptor-null (Prlr+/-) mice are glucose intolerant, had a lower number of beta cells and lower serum insulin levels than wild type mice during pregnancy. However, since Prlr expression is ubiquitous, to determine its beta-cell-specific effects, we generated a transgenic mouse with a floxed Prlr allele under the control of an inducible promoter, i.e. bPrlR-/- mice, allowing conditional deletion of Prlr from beta cells in adult mice. In this study, we found that beta-cell-specific Prlr reduction resulted in elevated blood glucose during pregnancy. Similar to our previous finding in mice with global Prlr reduction, beta-cell-specific Prlr loss led to a lower beta-cell mass and a lower in vivo insulin level during pregnancy. However, these islets do not have an intrinsic insulin secretion defect when tested in vitro. Interestingly, when we compared the islet gene expression profile, using islets isolated from mice with global versus beta-cell-specific Prlr reduction, we found differences in expression of genes that regulate apoptosis, synaptic vesicle function and neuronal development. Indeed, islets from pregnant Prlr+/- mice are more susceptible glucolipotoxicity than bPrlR+/- islets. These observations suggest that Prlr has both cell-autonomous and non-cell-autonomous effect on beta cells, beyond its regulation of pro-proliferative genes.
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| Overall design |
A total of 7 samples were included. Heterozygous whole body knock-out mice (N=3) obtained from Jackson Laboratory were used as a reference to compare to conditional Plr deletion in beta pancreatic cells (n=4). (Pdx1CreERTM:PrlR-/- ). Breifly, the confitional ready lines (Tm1a) were obtained from EUCOMM (The European Conditional Mouse Mutagenesis Program) and generated by breeding with FLPeR mice (The Jackson Laboratories) (Tm1c) and then Pdx1CreERTM mouse (from Mutant Mouse Resource & Research Centers supported by NIH, Stock No.:000350-UCD) (Tm1d). At 3-4 months of age, heterozygous whole-body and homozyous conditionally deleted Plr knock-out mice were bred to wild-type males and islets were isolated at gestational day 15.
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| Contributor(s) |
Shrivastava V, Lee M, Pretorius M, Radford B, Makkar G, Huang C |
| Citation(s) |
33990661 |
| Submission date |
Aug 24, 2020 |
| Last update date |
May 25, 2021 |
| Contact name |
Carol Huang |
| E-mail(s) |
Carol.Huang@albertahealthservices.ca
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| Phone |
403-210-3977
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| Organization name |
University of Calgary
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| Department |
Biochemistry and Molecular Biology
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| Street address |
3330 Hospital Dr NW
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| City |
Calgary |
| State/province |
AB |
| ZIP/Postal code |
T2N 4N1 |
| Country |
Canada |
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| Platforms (1) |
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| Samples (7)
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| Relations |
| BioProject |
PRJNA659005 |
| SRA |
SRP278641 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE156774_RAW.tar |
8.2 Mb |
(http)(custom) |
TAR (of TXT) |
| GSE156774_gene_fpkm.txt.gz |
910.5 Kb |
(ftp)(http) |
TXT |
| GSE156774_transcript_fpkm.txt.gz |
2.5 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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