Beta-cell ARNT is required for normal glucose tolerance in murine pregnancy.

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  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science
    • Subject Terms:
      Aryl Hydrocarbon Receptor Nuclear Translocator/*genetics ; Cyclin D2/*genetics ; Glucose/*metabolism ; Glucose Intolerance/*genetics ; Insulin-Secreting Cells/*metabolism; Animals ; Aryl Hydrocarbon Receptor Nuclear Translocator/metabolism ; Cell Proliferation ; Crosses, Genetic ; Cyclin D2/metabolism ; Female ; Gene Expression Regulation ; Glucose Intolerance/metabolism ; Glucose Intolerance/pathology ; Glucose-6-Phosphate Isomerase/genetics ; Glucose-6-Phosphate Isomerase/metabolism ; Insulin/metabolism ; Insulin Receptor Substrate Proteins/genetics ; Insulin Receptor Substrate Proteins/metabolism ; Insulin Secretion ; Insulin-Secreting Cells/pathology ; Male ; Mice ; Mice, Knockout ; Pregnancy
    • Abstract:
      Aims: Insulin secretion increases in normal pregnancy to meet increasing demands. Inability to increase beta-cell function results in gestational diabetes mellitus (GDM). We have previously shown that the expression of the transcription factor ARNT (Aryl-hydrocarbon Receptor Nuclear Translocator) is reduced in the islets of humans with type 2 diabetes. Mice with a beta-cell specific deletion of ARNT (β-ARNT mice) have impaired glucose tolerance secondary to defective insulin secretion. We hypothesised that ARNT is required to increase beta-cell function during pregnancy, and that β-ARNT mice would be unable to compensate for the beta-cell stress of pregnancy. The aims of this study were to investigate the mechanisms of ARNT regulation of beta-cell function and glucose tolerance in pregnancy.
      Methods: β-ARNT females were mated with floxed control (FC) males and FC females with β-ARNT males.
      Results: During pregnancy, β-ARNT mice had a marked deterioration in glucose tolerance secondary to defective insulin secretion. There was impaired beta-cell proliferation in late pregnancy, associated with decreased protein and mRNA levels of the islet cell-cycle regulator cyclinD2. There was also reduced expression of Irs2 and G6PI. In contrast, in control mice, pregnancy was associated with a 2.1-fold increase in ARNT protein and a 1.6-fold increase in cyclinD2 protein, and with increased beta-cell proliferation.
      Conclusions: Islet ARNT increases in normal murine pregnancy and beta-cell ARNT is required for cyclinD2 induction and increased beta-cell proliferation in pregnancy.
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    • Accession Number:
      0 (Arnt protein, mouse)
      0 (Ccnd2 protein, mouse)
      0 (Cyclin D2)
      0 (Insulin)
      0 (Insulin Receptor Substrate Proteins)
      0 (Irs2 protein, mouse)
      138391-32-9 (Aryl Hydrocarbon Receptor Nuclear Translocator)
      EC 5.3.1.9 (Glucose-6-Phosphate Isomerase)
      IY9XDZ35W2 (Glucose)
    • Publication Date:
      Date Created: 20131109 Date Completed: 20140802 Latest Revision: 20211021
    • Publication Date:
      20240628
    • Accession Number:
      PMC3812008
    • Accession Number:
      10.1371/journal.pone.0077419
    • Accession Number:
      24204824