Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA130715 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR064703.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:The insulin inhibitory receptor (inceptor) was recently identified as a key terminator of insulin and insulin-like growth factor 1 receptor (INSR/IGF1R) signaling in pancreatic ?-cells12. Yet, the relevance of ?-cell inceptor for glucose regulation through the INS1R/IGF1R axis has only been demonstrated for normoglycemic and insulin sensitive lean mice, questioning whether inceptor regulation of INS1R/IGF1R action also plays a role in glucose metabolism under conditions of diet-induced obesity and insulin resistance. Here we demonstrate that whole-body germline loss of inceptor improves glucose metabolism in diet-induced obese mice with only minimal effects on weight and body composition. To assess the effect in different tissues we performed proteomics in the global, neuronal and beta cell specific mouse knock-outs.
2024-01-17 | PXD046256 | Pride
Project description:1. evaluation of diagnostic importance of insulin like growth factor binding protein3 in patient with recently diagnosed as Colorectal cancer
2. correlation between the diagnostic efficacy of insulin like growth factor binding protein 3 with routine marker carcinoembryonic antigen.
| 59449 | ecrin-mdr-crc
Project description:Insulin analogues are designed to improve the pharmacokinetic parameters compared to regular human insulin. This provides a sustained control of blood glucose levels in diabetic patients. All novel insulin analogues are tested for their mitogenic side effects, however these assays do not take into account the molecular mode-of-action of different insulin analogues. Insulin analogues can bind the insulin receptor (INSR) and the insulin-like growth factor-1 receptor (IGF1R) with different affinities and consequently will activate different downstream signaling pathways. Here we used a panel of MCF7 human breast cancer cell lines that selectively express either one of the isoforms of the INSR (IRA or IRB) or the IGF1R. We sought to study the role of the different receptors (IRA, IRB and IGF1R) in the mitogenic signaling of insulin-like molecules (including insulin, glargine, X10 (or AspB10) and IGF1). MCF7 IRA, MCF7 IRB or MCF7 IGF1R cells (as described in Arch Toxicol. 2014 Apr;88(4):953-66. doi: 10.1007/s00204-014-1201-2. Epub 2014 Jan 25.) were cultured in RPMI supplemented with 5% (v/v) CDFBS (Hyclone) and used for experiments. Cells have been exposed for 1 or 6 hours to 10 nM of the indicated insulin-like molecule. As a control sample a vehicle stimulation was performed that contained everything except the active compound.
2015-01-29 | E-GEOD-65398 | biostudies-arrayexpress
Project description:We have previously determined the insulin-like growth factor 1 receptor (IGF1R) to be amplified and overexpressed in paediatric glioblastoma. In order to probe the efficacy and mechanisms of action of various inhibitors of the receptor, we have carried out expression profiling of paediatric glioblastoma cells treated with 5x IC50 of the compounds PPP and NVP-AEW541 over a 24 hour time-course.
2011-01-08 | E-TABM-889 | biostudies-arrayexpress
Project description:We have previously determined the insulin-like growth factor 1 receptor (IGF1R) to be amplified and overexpressed in Wilms tumour. In order to probe the efficacy and mechanisms of action of various inhibitors of the receptor, we have carried out expression profiling of Wilms tumour cells treated with 5x IC50 of the compounds PPP and NVP-AEW541 over a 24 hour time-course.
2011-01-08 | E-TABM-891 | biostudies-arrayexpress
Project description:Insulin analogues are designed to improve the pharmacokinetic parameters compared to regular human insulin. This provides a sustained control of blood glucose levels in diabetic patients. All novel insulin analogues are tested for their mitogenic side effects, however these assays do not take into account the molecular mode-of-action of different insulin analogues. Insulin analogues can bind the insulin receptor (INSR) and the insulin-like growth factor-1 receptor (IGF1R) with different affinities and consequently will activate different downstream signaling pathways. Here we used a panel of MCF7 human breast cancer cell lines that selectively express either one of the isoforms of the INSR (IRA or IRB) or the IGF1R. We sought to study the role of the different receptors (IRA, IRB and IGF1R) in the mitogenic signaling of insulin-like molecules (including insulin, glargine, X10 (or AspB10) and IGF1).
2015-01-29 | GSE65398 | GEO
Project description:Bianconi2012 - EGFR and IGF1R pathway in lung cancer
EGFR and IGF1R pathways play a key role in various human cancers and are crucial for tumour transformation and survival of malignant cells. High EGFR and IGF1R expression and activity has been associated with multiple aspects of cancer progression including tumourigenesis, metastasis, resistance to chemotherapeutics and other molecularly targeted drugs. Here, the biological relationship between the proteins involved in EGFR and IGF1R pathways and the downstream MAPK and PIK3 networks has been modelled to study the time behaviour of the overall system, and the functional interdependencies among the receptors, the proteins and kinases involved.
This model is described in the article:
Computational model of EGFR and IGF1R pathways in lung cancer: a Systems Biology approach for Translational Oncology.
Bianconi F, Baldelli E, Ludovini V, Crinò L, Flacco A, Valigi P.
Biotechnol Adv. 2012 Jan-Feb;30(1):142-53.
Abstract:
In this paper we propose a Systems Biology approach to understand the molecular biology of the Epidermal Growth Factor Receptor (EGFR, also known as ErbB1/HER1) and type 1 Insulin-like Growth Factor (IGF1R) pathways in non-small cell lung cancer (NSCLC). This approach, combined with Translational Oncology methodologies, is used to address the experimental evidence of a close relationship among EGFR and IGF1R protein expression, by immunohistochemistry (IHC) and gene amplification, by in situ hybridization (FISH) and the corresponding ability to develop a more aggressive behavior. We develop a detailed in silico model, based on ordinary differential equations, of the pathways and study the dynamic implications of receptor alterations on the time behavior of the MAPK cascade down to ERK, which in turn governs proliferation and cell migration. In addition, an extensive sensitivity analysis of the proposed model is carried out and a simplified model is proposed which allows us to infer a similar relationship among EGFR and IGF1R activities and disease outcome.
This model is hosted on BioModels Database
and identified by: MODEL1209230000
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
2024-09-02 | BIOMD0000000427 | BioModels
Project description:Resistance to insulin and insulin-like growth factor 1 (IGF1) in pancreatic β-cells causes overt diabetes in mice; thus, therapies that sensitize β-cells to insulin may protect patients with diabetes against β-cell failure. Here we identify an inhibitor of insulin receptor (INSR) and IGF1 receptor (IGF1R) signalling in mouse β-cells, which we name the insulin inhibitory receptor (inceptor; encoded by the gene Iir). Inceptor contains an extracellular cysteine-rich domain with similarities to INSR and IGF1R4, and a mannose 6-phosphate domain that is also found in the IGF2 receptor (IGF2R)5. Knockout mice that lack inceptor (Iir-/-) exhibit signs of hyperinsulinaemia and hypoglycaemia, and die within a few hours of birth. Molecular and cellular analyses of embryonic and postnatal pancreases from Iir-/- mice showed an increase in the activation of INSR–IGF1R in Iir-/- pancreatic tissue, resulting in an increase in the proliferation and mass of β-cells. Similarly, inducible β-cell-specific Iir-/- knockout in adult mice and in ex vivo islets led to an increase in the activation of INSR–IGF1R and increased proliferation of β-cells, resulting in improved glucose tolerance in vivo. Mechanistically, inceptor interacts with INSR–IGF1R to facilitate clathrin-mediated endocytosis for receptor desensitization. Blocking this physical interaction using monoclonal antibodies against the extracellular domain of inceptor resulted in the retention of inceptor and INSR at the plasma membrane to sustain the activation of INSR–IGF1R in β-cells. Together, our findings show that inceptor shields insulinproducing β-cells from constitutive pathway activation, and identify inceptor as a potential molecular target for INSR–IGF1R sensitization and diabetes therapy.
2021-01-27 | GSE144519 | GEO
Project description:Diabetic nephropathy is a major cause of end-stage renal disease. Kidney podocytes play a central role in the pathogenesis of diabetic nephropathy. With their intercellular contacts they assemble part of the kidney filter. Many molecular mechanisms of the pathogenesis of diabetic nephropathy are not elucidated and targeted therapies are lacking. Nephron-specific TrkCknockout (TrkC-KO) and TrkC overexpressing mice exhibit features of diabetic nephropathy such as enlarged glomeruli with mesangial proliferation, basement membrane thickening, albuminuria and podocyte loss when aging. Insulin-like growth factor 1 receptor (Igf1R)- associated gene expression was regulated in TrkC-KO mice glomeruli by qPCR. Phosphoproteins associated with insulin, erb-b2 receptor tyrosine kinase (Erbb) and Toll-like receptor signaling were enriched in lysates of podocytes treated with the TrkC ligand neurotrophin-3(Nt-3) in a mass spectrometry analysis. Activation of TrkC by Nt-3 resulted in phosphorylation of the Igf1R on activating tyrosine residues in podocytes. Our results identify TrkC to be a potentially targetable mediator of diabetic nephropathy.
2021-09-10 | PXD017960 | Pride
Project description:IGF1 and IGF1 receptors (IGF1R) are present in the adult heart and have been shown to be essential for myocardial performance. Insulin-like growth factor 1 (IGF1) is produced in numerous tissues particularly by the liver in response to growth hormone stimulation and is an important factor in the regulation of post-natal growth and development. We have generated and characterized transgenic mice over-expressing the IGF1R. We crossed IGF1R transgenic mice with dominant negative (dn)PI3K (p110) and with constitutively active (ca)PI3K(p110) transgenic mice. Expression profiling was performed on the ventricles of IGF1R, IGF1R-caPI3K, IGF1R-dnPI3K, caPI3K, dnPI3K transgenic female mice at 3 months of age. Non-transgenic littermates were used as controls.
2007-09-29 | E-GEOD-1143 | biostudies-arrayexpress