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Gene expression in response to short and long term cAMP stimulation in the INS-1 insulinoma cell line

ABSTRACT: Long term exposure to incretin hormones is known to have salutory effects on beta cell function and viability. While short-term cAMP induction is known to have a signature CREB-CRTC target gene response, the long-term effects of cAMP on beta cell gene expression are less well understood. We used rat microarray analysis to compare the genome-wide gene expression response to short-term (2 hours) and long-term (16 hours) stimulations of the cAMP agonist forskolin in INS-1 insulinoma cells. INS-1 cells were exposed to forskolin for 2 or 16 hours in RPMI medium containing 10% serum. Control samples wer incubated for the same time without forskolin. Extracted RNA was used for hybridization on Affymetrix rat 1.0 st gene arrays.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Sam Van de Velde

PROVIDER: E-GEOD-31736 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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mTOR links incretin signaling to HIF induction in pancreatic beta cells.

Van de Velde Sam S Hogan Meghan F MF Montminy Marc M

Proceedings of the National Academy of Sciences of the United States of America 20110926 41

Under feeding conditions, the incretin hormone GLP-1 promotes pancreatic islet viability by triggering the cAMP pathway in beta cells. Increases in PKA activity stimulate the phosphorylation of CREB, which in turn enhances beta cell survival by upregulating IRS2 expression. Although sustained GLP-1 action appears important for its salutary effects on islet function, the transient nature of CREB activation has pointed to the involvement of additional nuclear factors in this process. Following the ...[more]

PMID: 21949366

Similar Datasets

Gene expression in response to short and long term cAMP stimulation in the INS-1 insulinoma cell line

Project description:Long term exposure to incretin hormones is known to have salutory effects on beta cell function and viability. While short-term cAMP induction is known to have a signature CREB-CRTC target gene response, the long-term effects of cAMP on beta cell gene expression are less well understood. We used rat microarray analysis to compare the genome-wide gene expression response to short-term (2 hours) and long-term (16 hours) stimulations of the cAMP agonist forskolin in INS-1 insulinoma cells.

2011-11-22 | GSE31736 | GEO

Progressive ER stress over time due to human insulin gene mutation contributes to pancreatic β-cell dysfunction, islet inflammation and compensatory responses

Project description:Heterozygous human INS gene mutations are known to promote ER stress, leading to β-cell dysfunction and neonatal diabetes. Recent literature challenged the long-standing notion that neonatal diabetes occurs due to ER stress-induced β-cell apoptosis. Importantly, mechanisms of β-cell failure during the disease progression and why the other wild-type (WT) INS allele is unable to function still remain unclear. Here, our computational modelling studies, short-term and long-term expression studies in β-cells revealed the presence of ER stress, organelle changes and insulin processing defects, resulting in decreased insulin secretion but not insulin secretory capacity. By nine weeks of expression of mutant INS, dominant negative effects of mutant INS were evident and β-cell insulin secretory capacity declined. INS+/C109Y patient-derived β-like cells and single cell RNA-Sequencing analyses then revealed compensatory upregulation in genes involved in insulin secretion, processing and inflammatory response. Our results provide deeper insights into the mechanisms of β-cell failure during INS mutation-mediated diabetes disease progression. Decreasing CHOP-10, sXBP1 or inflammatory response could be avenues to restore the function of the remaining WT INS allele.

2021-10-03 | GSE141319 | GEO

Expression of Cyclic AMP associated genes on primary culture human myometrial cells

Project description:During pregnancy, the myometrium remains quiescent but at term, switches to a state capable of producing a series of coordinated contractions for the delivery of the fetus. Myometrial contractions of labour signify the normal physiological end-point of pregnancy but the biochemical onset of labour may occur at or before term via a series of changes in expression of labour associated genes that are responsible for controlling the activity of the uterus during pregnancy and parturition. There is increasing evidence that components of the cAMP-signalling pathway are up-regulated in the human myometrium during pregnancy to promote the relaxation of the myometrium until term. Our aim was to determine which cAMP-associated genes are important during pregnancy and parturition by exposing myometrial cells to forskolin and performing an a gene array. We then plan to study the trend of the cAMP-associated genes at different stages of gestation and during labour. In this study, we used microarrays to elucidate forskolin responsive genes in human myometrium. These data may provide a broader view of gene networks and cellular functions regulated by forskolin in human myometrial cells. In our future study, this will also help us understand the role of cAMP in human parturition. Primary cultures of human myometrial cells were grown from myometrial biopsies obtained at the time of elective caesarean section at term. Cells were exposed to forskolin (100 ÂµM) for 48 hours, and then total RNA were extracted from each culture. Two comparisons were carried out including: 1. Control 2. Forksolin

2016-07-01 | E-GEOD-75799 | biostudies-arrayexpress

Rattus norvegicus

Project description:Gene expression in response to short and long term cAMP stimulation in the INS-1 insulinoma cell line

| PRJNA145433 | ENA

PTHRP/Adenylate cyclase promotes parietal whereas Wnt/β-catenin signaling promotes visceral endoderm differentiation of rat XEN cells.

2013-02-01 | GSE42438 | GEO

PTHRP/Adenylate cyclase promotes parietal whereas Wnt/β-catenin signaling promotes visceral endoderm differentiation of rat XEN cells.

Project description:In this study we showed that rat XEN cells grown in the presence of a GSK3 inhibitor exhibited enhanced formation of cell contacts and decreased motility. In contrast, treatment with forskolin induced the PE formation and epithelial-mesenchymal transition (EMT) in rat XEN cells. Using microarray and real-time PCR assays, we found that VE versus PE formation of rat XEN cells was correlated with change in expression levels of VE or PE marker genes. Similar to forskolin, EMT was prompted upon treatment of rat XEN cells with recombinant parathyroid hormone related peptide (PTHRP), an activator of the cAMP pathway in vivo. Taken together, our data suggest that rat XEN cells are PrE-like cells. The activation of Wnt pathway in rat XEN cells leads to the acquisition of VE characteristics, whereas the activation of the PTHRP/cAMP pathway leads to EMT and the formation of PE. Rat XEN cells were cultured in four different conditions with 3 parallels for each condition: (1-3) without treatments control, (4-6) 2 days treated with CHIR alone, (7-9) 1 day treated with CHIR and 1 day with both CHIR and forskolin, and (10-12) 1 day treated with forskolin alone. In all samples on DAY1 cells were plated, at DAY2 cells were cultured in usual conditions (DMEM F12 medium and 10% Fetal Bovine Serum, both from Sigma) and inhibitor of GSK3 kinase 3 μM CHIR99021 (Axon Medchem) was added in samples 4-9. On DAY3 all cells were cultured in medium with 0.1% serum to exclude the influence of serum and in CONTROL (1-3) cells were cultured without experimental treatments, in CHIR (4-6) cells were further cultured with 3 μM CHIR99021, in CHIR plus FORSKOLIN cells were cultured with 3 μM CHIR99021 and 10μM Forskolin (Sigma), in FORSKOLIN cells were cultured for 1 day with 10 μM Forskolin. On DAY4 RNA was isolated.

2013-02-01 | E-GEOD-42438 | biostudies-arrayexpress

Expression of Cyclic AMP associated genes on primary culture human myometrial cells

2016-07-01 | GSE75799 | GEO

ChIP-Seq analysis of transcription factors CREB and C/EBP beta in vasopressin-responsive mouse renal collecting duct mpkCCD cells

Project description:Vasopressin, a peptide hormone, controls renal water excretion, largely through regulation of water channel aquaporin-2 (AQP2) in the renal collecting duct. There are two regulatory mechanisms of AQP2: 1) short-term regulation by membrane trafficking of AQP2; and 2) long-term regulation involving vasopressin-induced changes of protein abundance of AQP2 through regulation of gene transcription and protein half-life. Vasopressin binds a G protein-coupled receptor (V2R) activating a cyclic AMP/protein kinase A (PKA) signaling pathway. Sequentially, after activation of cAMP/PKA signaling, many of transcription factors involve gene transcription process. cAMP-response element binding protein (CREB) and cAMP-responsive transcription factor C/EBP beta are potential candidates for vaopressin-mediated regulation of Aqp2 gene transcription proviously reported. In the present study, genome-wide binding sites for two b-ZIP transcription factors CREB and C/EBP beta were identified in vasopressin-responsive mouse collecting duct mpkCCD cells using ChIP-Seq.

2018-03-26 | GSE98076 | GEO

Insulin Receptor-Overexpressing beta-Cells Ameliorate Hyperglycemia in Diabetic Rats through Wnt Signaling Activation

Project description:To investigate the therapeutic efficacy of beta-cells with IR manipulation, a plasmid containing human IR was stably introduced into rat beta-cell line INS-1 cells (namely, INS-IR cells). In the INS-IR cells, the role of cross-talk between insulin and Wnt signaling pathways in improving the functionality of beta-cells was investigated.

2013-06-11 | E-MEXP-3836 | biostudies-arrayexpress

Time- and dose-resolved proteome of PM2.5 exposure in rat model

Project description:this paper used Mass spectrometry, Fast-seq, and catTFRE to study the pattern of 6316 proteins as well as 387 Transcription factors associated with PM2.5 in both short-term and long-term rat injury models.

2020-05-27 | PXD019404 |

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