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http://purl.uniprot.org/citations/15605246http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/15605246http://www.w3.org/2000/01/rdf-schema#comment"

Aim/hypothesis

Maturation 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.

Methods

Transcriptome 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.

Results

During 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/interpretation

These 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."xsd:string
http://purl.uniprot.org/citations/15605246http://purl.org/dc/terms/identifier"doi:10.1007/s00125-004-1578-1"xsd:string
http://purl.uniprot.org/citations/15605246http://purl.uniprot.org/core/author"Nielsen K."xsd:string
http://purl.uniprot.org/citations/15605246http://purl.uniprot.org/core/author"Wang H."xsd:string
http://purl.uniprot.org/citations/15605246http://purl.uniprot.org/core/author"Kruhoffer M."xsd:string
http://purl.uniprot.org/citations/15605246http://purl.uniprot.org/core/author"Karlsen A.E."xsd:string
http://purl.uniprot.org/citations/15605246http://purl.uniprot.org/core/author"Nerup J."xsd:string
http://purl.uniprot.org/citations/15605246http://purl.uniprot.org/core/author"Orntoft T."xsd:string
http://purl.uniprot.org/citations/15605246http://purl.uniprot.org/core/author"Jorgensen M.C."xsd:string
http://purl.uniprot.org/citations/15605246http://purl.uniprot.org/core/author"Wollheim C."xsd:string
http://purl.uniprot.org/citations/15605246http://purl.uniprot.org/core/author"Sparre T."xsd:string
http://purl.uniprot.org/citations/15605246http://purl.uniprot.org/core/date"2004"xsd:gYear
http://purl.uniprot.org/citations/15605246http://purl.uniprot.org/core/name"Diabetologia"xsd:string
http://purl.uniprot.org/citations/15605246http://purl.uniprot.org/core/pages"2185-2199"xsd:string
http://purl.uniprot.org/citations/15605246http://purl.uniprot.org/core/title"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."xsd:string
http://purl.uniprot.org/citations/15605246http://purl.uniprot.org/core/volume"47"xsd:string
http://purl.uniprot.org/citations/15605246http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/15605246
http://purl.uniprot.org/citations/15605246http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/15605246
http://purl.uniprot.org/uniprot/#_P52947-mappedCitation-15605246http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15605246
http://purl.uniprot.org/uniprot/#_A6K1A7-mappedCitation-15605246http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15605246
http://purl.uniprot.org/uniprot/A6K1A7http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/15605246
http://purl.uniprot.org/uniprot/P52947http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/15605246