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Transient fetal defects in islet architecture caused by pancreas-specific deletion of Bmpr1a led to ageing glucose intolerance

ABSTRACT: Microarray raw data were generated from RNA extracted from isolated islets of 12-week wild type or Pdx1-controled bone morphogenetic protein receptor 1a gene knockout mice Analysis were performed on data generated from RNA extracted from isolated islets of 12-week wild type or Pdx1-controled bone morphogenetic protein receptor 1a gene knockout mice

ORGANISM(S): Mus musculus

SUBMITTER: Abdul Baten

PROVIDER: E-GEOD-41699 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Transient fetal defects in islet architecture caused by pancreas-specific deletion of Bmpr1a led to ageing glucose intolerance

Project description:Microarray raw data were generated from RNA extracted from isolated islets of 12-week wild type or Pdx1-controled bone morphogenetic protein receptor 1a gene knockout mice

2012-11-26 | GSE41699 | GEO

Identification of Nkx6.1 regulated genes in mature pancreatic islets.

Project description:Nkx6.1 target genes were identified in mature pancreatic islets by comparing gene expression in conditional Nkx6.1-ablated islets versus control islets using microarray analysis. Nkx6.1 was conditionally ablated in mature pancreatic islets by recombination of a Nkx6.1-flox allele using the tamoxifen-inducible Pdx1-CreERTM allele (Gu et al 2002). Mice were injected with 2 mg/25 g tamoxifen in corn oil four times between 4 and 6 weeks of age. Islets were isolated after the final tamoxifen injection. Total RNA was isolated and pooled from pancreata of 6 week old Nkx6.1fl/-;Pdx1-CreERTM (mutant) versus Nkx6.1fl/+;Pdx1-CreERTM (control) littermates for 3 biological replicates.

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Expression data from islets of Pdx1-creLate, control and pregnant mice

Project description:ABSTRACT: The human growth hormone (hGH) minigene is frequently used in transgenic mouse lines to ensure proper transgene expression. Here, we show that hGH is expressed in islets isolated from the commonly used Pdx1-CreLate mouse model. Locally secreted hGH activates prolactin receptors on M-NM-2 cells causing phosphorylation of STAT5, and induces a pregnancy-like change in gene expression, augmented pancreatic M-NM-2 cell mass and insulin content. In addition, islets of Pdx1-CreLate mice had lower GLUT2 expression, reduced glucose-induced insulin release and were protected against the M-NM-2 cell toxin streptozotocin. As the hGH minigene is commonly used in a great number of Cre-driver and other transgenic mouse models in diabetes research, the currently reported profound phenotypic changes may necessitate the re-evaluation of a large amount of previously published work. 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). Islets were isolated from Pdx1-creLate, control and pregnant mice for RNA extraction and hybridization on Affymetrix microarrays. For every condition, at least 3 biological replicates were used.

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The Pdx1 Cistrome of Pancreatic Islets

Project description:We performed global location analysis of Pdx1 occupancy in mouse and human islets.

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The Pdx1 Cistrome of Pancreatic Islets

Project description:The Pdx1 Cistrome of Pancreatic Islets

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Expression data from islets of Pdx1-creLate, control and pregnant mice

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

Robust Differentiation of Islet Progenitors into Functional Insulin-secreting Cells by Suppression of Key Transcription Regulators

Project description:Gene profiling revealed that differentiation was accompanied by suppression of a range of transcription regulator genes typical of islet progenitor cells. In order to understand molecular mechanisms of differentiation, transcriptome-wide gene expression analysis was performed on purified islet progenitors at days 0, 1 and 4 of differentiation together with adult islets as a control. In order to understand molecular mechanisms of differentiation, transcriptome-wide gene expression analysis was performed on purified islet progenitors at days 0, 1 and 4 of differentiation together with adult islets as a control.

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Transcription profiling by array of human pacreatic islets prepared for clinical transplantation

Project description:This study compared 9 human islet preparations, extracted and prepared for clinical transplantation. Human islets were isolated as, and all were of transplant quality. Unamplified RNA was extracted and hybridized to Affymetrix HGU133+2 arrays. By using gene set enrichment analysis to investigate the variability of each probeset on the array, it was clear that isolated human islets undergo varying degrees of hypoxic stress. Further to this, key glycolytic genes, all of which are under the control of hypoxia inducing factor 1a (HIF-1a) were activated, indicating a switch towards anareobic glycolysis. Glycolysis severely impairs the ability of islets to sense glucose and secrete insulin in response to elevated blood sugar. We confirmed these findings in mouse rodents, demonstrated a dependance upon HIF-1a, and showed that even after 4 weeks, hypoxic islets retained their glycolytic molecular profile.

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