ArticleDiabetologia2004
Gene expression profiles during beta cell maturation and after IL-1beta exposure reveal important roles of Pdx-1 and Nkx6.1 for IL-1beta sensitivity.
Article in Diabetologia, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Expression of the ZIP/SLC39A transporters in β-cells: a systematic review and integration of multiple datasets.BMC genomics · 2017Pooled it
- Temporal Transcriptome Analysis Reveals Dynamic Gene Expression Patterns Driving β-Cell Maturation.Frontiers in cell and developmental biology · 2021Article
- MicroRNAs: Novel Players in the Dialogue between Pancreatic Islets and Immune System in Autoimmune Diabetes.BioMed research international · 2015Review
- Article
- Review
- Independent component and pathway-based analysis of miRNA-regulated gene expression in a model of type 1 diabetes.BMC genomics · 2011Article
- Novel monoclonal antibodies against Pdx1 reveal feedback regulation of Pdx1 protein levels.European journal of histochemistry : EJH · 2010Article
- Zinc transporter gene expression is regulated by pro-inflammatory cytokines: a potential role for zinc transporters in beta-cell apoptosis?BMC endocrine disorders · 2009Article
- The intrauterine metabolic environment modulates the gene expression pattern in fetal rat islets: prevention by maternal taurine supplementation.Diabetologia · 2008Article
- Posttranslational Protein Modifications in Type 1 Diabetes - Genetic Studies with PCMT1, the Repair Enzyme Protein Isoaspartate Methyltransferase (PIMT) Encoding Gene.The review of diabetic studies : RDS · 2008Article
- Transcriptional profiling of type 1 diabetes genes on chromosome 21 in a rat beta-cell line and human pancreatic islets.Genes and immunity · 2007Article
- Post-translational protein modifications in type 1 diabetes: a role for the repair enzyme protein-L-isoaspartate (D-aspartate) O-methyltransferase?Diabetologia · 2007Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aim/hypothesisMaturation of the beta cells in the islets of Langerhans is dependent upon sequential activation of different transcription factors such as Pdx-1 and Nkx6.1. This maturation is associated with an acquired sensitivity to cytokines and may eventually lead to type 1 diabetes. The aims of this study were to characterise changes in mRNA expression during beta cell maturation as well as after interleukin-1beta (IL-1beta) exposure.
methodsTranscriptome analyses were performed on two phenotypes characterised as a glucagon-producing pre-beta-cell phenotype (NHI-glu), which matures to an IL-1beta-sensitive insulin-producing beta cell phenotype (NHI-ins). Beta cell lines over-expressing Pdx-1 or Nkx6.1, respectively, were used for functional characterisation of acquired IL-1beta sensitivity.
resultsDuring beta cell maturation 98 fully annotated mRNAs changed expression levels. Of these, 50 were also changed after 24 h of IL-1beta exposure. In addition, 522 and 197 fully annotated mRNAs, not affected by maturation, also changed expression levels following IL-1beta exposure of the beta cell and the pre-beta-cell phenotype, respectively. Beta cell maturation was associated with an increased expression of Nkx6.1, whereas both Pdx-1 and Nkx6.1 expression were decreased following IL-1beta exposure. Over-expression of Nkx6.1 or Pdx-1 in cell lines resulted in a significantly increased sensitivity to IL-1beta. CONCLUSIONS/
interpretationThese results suggest that the final beta cell maturation accompanied by increased IL-1beta sensitivity is, in part, dependent upon the expression of genes regulated by Pdx-1 and Nkx6.1. Future classification of the genes regulated by these transcription factors and changed during beta cell maturation should elucidate their role in the acquired sensitivity to IL-1beta and may be helpful in identifying new targets for intervention/prevention strategies.
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