Mouse pancreatic islets during pregnancy
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE22125 | GEO | 2010/06/04
SECONDARY ACCESSION(S): PRJNA127593
REPOSITORIES: GEO
Similar Datasets
Project description:During pregnancy, pancreatic islets undergo structural and functional changes that lead to enhance insulin release in response to increased insulin demand, which is rapidly reversed at parturition. One of the most important changes is expansion of pancreatic β-cell mass mainly by increased proliferation of β cells. We used microarrays to detail the global programme of gene expression and identified distinct up- or down-regulated genes during pregnancy. Maternal islet were isolated from mice at dpc 0 and 12.5 dpc of pregnancy for RNA extraction and hybridization on Affymetrix microarrays. We sought to identify the responsible factors for the proliferation of islets during pregnancy.
2010-06-16 | E-GEOD-22125 | biostudies-arrayexpress
Project description:During pregnancy, the energy requirements of the fetus impose changes in maternal metabolism. Increasing insulin resistance in the mother maintains nutrient flow to the growing fetus, while prolactin and placental lactogen counterbalance this resistance and prevent maternal hyperglycemia by driving expansion of the maternal population of insulin-producing beta-cells. However, the exact mechanisms by which the lactogenic hormones drive beta-cell expansion remain uncertain. Here we show that serotonin acts downstream of lactogen signaling to drive beta-cell proliferation. Serotonin synthetic enzyme Tph1 and serotonin production increased sharply in beta-cells during pregnancy or after treatment with lactogens in vitro. Inhibition of serotonin synthesis by dietary tryptophan restriction or Tph inhibition blocked beta-cell expansion and induced glucose intolerance in pregnant mice without affecting insulin sensitivity. Expression of the Gq-linked serotonin receptor Htr2b in maternal islets increased during pregnancy and normalized just prior to parturition, while expression of the Gi-linked receptor Htr1d increased at the end of pregnancy and postpartum. Blocking Htr2b signaling in pregnant mice also blocked beta-cell expansion and caused glucose intolerance. These studies reveal an integrated signaling pathway linking beta-cell mass to anticipated insulin need during pregnancy. Modulators of this pathway, including medications and diet, may affect the risk of gestational diabetes. Analysis of poly(A)+ RNA from 3 biological replicates of pancreatic islets isolated from normal female and pregnant female mice
2010-07-01 | E-GEOD-21860 | biostudies-arrayexpress
Project description:The inability of the beta-cell to meet the demand for insulin brought about by insulin resistance leads to type 2 diabetes. In adults, beta-cell replication is one of the mechanisms thought to cause the expansion of beta-cell mass. Efforts to treat diabetes require knowledge of the pathways that drive facultative beta-cell proliferation in vivo. A robust physiological stimulus of beta-cell expansion is pregnancy, and identifying the mechanisms underlying this stimulus may provide therapeutic leads for the treatment of type 2 diabetes. The peak in beta-cell proliferation during pregnancy occurs on day 14.5 of gestation in mice. Using advanced genomic approaches, we globally characterize the gene expression signature of pancreatic islets on day 14.5 of gestation during pregnancy. We identify a total of 1,907 genes as differentially expressed in the islet during pregnancy. We demonstrate that the islet's ability to compensate for relative insulin deficiency during metabolic stress is associated with the induction of both proliferative and survival pathways. A comparison of the genes induced in three different models of islet expansion suggests that diverse mechanisms can be recruited to expand islet mass. The identification of many novel genes involved in islet expansion during pregnancy provides an important resource for diabetes researchers to further investigate how these factors contribute to the maintenance of not only islet mass, but ultimately beta-cell mass.
2010-06-26 | E-MTAB-120 | biostudies-arrayexpress
Project description:Pancreatic islets adapt to the increase in insulin demand during pregnancy by up-regulating beta cell proliferation, insulin synthesis, and lowering the threshold of glucose-stimulated insulin secretion. In vitro studies suggest that pregnancy hormones, such as placental lactogens and prolactin, both act through the prolactin receptor, are required for these adaptation. Furhtermore, we found that transgenic mice with heterogenous prolactin receptor null mutation are glucose intolerant, with a lower beta-cell mass and lower insulin levels. The goal here is to discover novel targets of prolactin receptor signaling in pancreatic beta cells during pregnancy.
2019-02-01 | GSE125350 | GEO
Project description:During pregnancy, the energy requirements of the fetus impose changes in maternal metabolism. Increasing insulin resistance in the mother maintains nutrient flow to the growing fetus, while prolactin and placental lactogen counterbalance this resistance and prevent maternal hyperglycemia by driving expansion of the maternal population of insulin-producing beta-cells. However, the exact mechanisms by which the lactogenic hormones drive beta-cell expansion remain uncertain. Here we show that serotonin acts downstream of lactogen signaling to drive beta-cell proliferation. Serotonin synthetic enzyme Tph1 and serotonin production increased sharply in beta-cells during pregnancy or after treatment with lactogens in vitro. Inhibition of serotonin synthesis by dietary tryptophan restriction or Tph inhibition blocked beta-cell expansion and induced glucose intolerance in pregnant mice without affecting insulin sensitivity. Expression of the Gq-linked serotonin receptor Htr2b in maternal islets increased during pregnancy and normalized just prior to parturition, while expression of the Gi-linked receptor Htr1d increased at the end of pregnancy and postpartum. Blocking Htr2b signaling in pregnant mice also blocked beta-cell expansion and caused glucose intolerance. These studies reveal an integrated signaling pathway linking beta-cell mass to anticipated insulin need during pregnancy. Modulators of this pathway, including medications and diet, may affect the risk of gestational diabetes.
2010-07-02 | GSE21860 | GEO
Project description: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.
2020-08-25 | GSE156774 | GEO
Project description:ABSTRACT: The human growth hormone (hGH) minigene is frequently used in the derivation of transgenic mouse lines to enhance transgene expression. Although this minigene is present in the transgenes as a secondcistron, and thus not thought to be expressed, we found that three commonly used lines, Pdx1-CreLate, RIP-Cre, and MIP-GFP, each expressed significant amounts of hGH in pancreatic islets. Locally secreted hGH binds to prolactin receptors on β cells, activates STAT5 signaling, and induces pregnancy-like changes in gene expression, thereby augmenting pancreatic β cell mass and insulin content. In addition, islets of Pdx1-CreLate mice have lower GLUT2 expression and reduced glucose-induced insulin release and are protected against the β cell toxin streptozotocin. These findings may be important when interpreting results obtained when these and other hGH minigene-containing transgenic mice are used. Data obtained for the Pdx1-creLate and control samples were compaired to investigate the effect of hGH on the mRNA profile of islets. The data obtained from the islets of pregnant mice was added to the analysis to confirm the pregnacy-like phenotype in the Pdx1-creLate islets. The data of the different days of pregnancy was already described in Schraenen et al. 2010 (PMID: 20886204 and PMID: 20938637).
2014-02-14 | GSE50851 | GEO
Project description:Pancreatic β-cell mass expands during pregnancy and regresses in the postpartum period in conjunction with dynamic metabolic demands on maternal glucose homeostasis. To understand transcriptional changes driving these adaptations in β-cells and other islet cell types, we performed single-cell RNA sequencing on islets from virgin, late gestation, and early postpartum mice. We identified transcriptional signatures unique to gestation and the postpartum in β-cells, including induction of the AP-1 transcription factor subunits and other genes involved in the immediate-early response (IEGs). Additionally, we found pregnancy and postpartum-induced changes differed within each endocrine cell type, and in endothelial cells and macrophages within islets. Together, our data reveal novel insights into cell-type specific transcriptional changes responsible for adaptations by islet cells to pregnancy and their resolution postpartum.
2023-03-07 | GSE226788 | GEO
Project description:Zinc finger protein ZBTB20 plays a critical role in regulating insulin expression from islet beta-cells by orchestrating their gene expression profile. We used microarrays to investigate the target gene of ZBTB20 in mouse pancreatic beta-cells. Adult mouse islets were harvested for RNA extraction and hybridization on Affymetrix microarrays. We sought to identify the target genes of transcription factor ZBTB20 in beta-cells. To that end, we isolated the islets from adult beta cell-specific ZBTB20 knockout and their littermate control mice.
2014-09-01 | E-GEOD-31961 | biostudies-arrayexpress
Project description:Maternal low-protein diet increases the susceptibility of offspring to type 2 diabetes. An insult to the pancreas during development can have long-term consequences on ?-cell mass and function. Because nutrients and growth factors signaling converge on mTOR, we hypothesized that mTOR plays a central role in ?-cell programming during fetal development. In this study, we revealed that newborns of dams exposed to low-protein diet (LP0.5) throughout pregnancy exhibited decreased insulin levels, ?-cell fraction, and mTOR signaling. Adult LP0.5 offspring demonstrated enhanced insulin sensitivity but remained glucose intolerant due to an insulin secretory defect and not reduced ?-cell mass. The insulin secretory defect was distal to Ca2+ influx, at the level of proinsulin biosynthesis and insulin content. LP0.5 islets exhibited reduced mTOR protein and increased expression of specific microRNAs. The reductions in mTOR protein and insulin secretion in LP0.5 islets were restored to normal by blockade of microRNAs 199a-3p and 342. Finally, transient activation of mTORC1 signaling in ?-cells during the last week of pregnancy rescued the neonatal ?-cell fraction defect and metabolic abnormalities in LP0.5 mice. These findings identify a major role of microRNAs and mTOR in ?-cell programing by maternal low-protein diet. To investigate which microRNAs are altered in islets isolated from 2-3 months old male offspring of dams fed low-protein diet (LP0.5) or control diet throughout pregnancy Pancreatic islets were isolated from 2-3 months old male offspring of dams fed low-protein diet (LP0.5) or control diet throughout pregnancy. Islets were isolated by collagenase digestion. The pancreas was perfused via the common duct with 1 mg/ml collagenase XI (Sigma-Aldrich) in HBSS (Life Technologies). Pancreatic digestion was carried out at 37 °C for 15 min, after which cold HBSS with 2.5% FBS (Life Technologies) was added. The suspension was centrifuged at 1000 rpm for 30s, washed 3 times with HBSS with 2.5% FBS, resuspended in RPMI complete media (RPMI 1640 with 5 mM Glucose, 10% FBS,100 IU/ml penicillin, 100 g/ml streptomycin) and poured onto a 70 µm cell strainer (BD Falcon, BD Biosciences). Islets were rinsed and handpicked. Islets were allowed to recover overnight in RPMI complete media before RNA isolation using MirVana Kit (Life Technologies).
2014-07-11 | E-GEOD-59279 | biostudies-arrayexpress