Beta-Cell ARNT Is Required for Normal Glucose Tolerance in Murine Pregnancy
| Autor: | Mark McLean, Jenny E. Gunton, Ayesha Karunatillake, Sue Mei Lau, Kim Cheng, N. W. Cheung, Rebecca A. Stokes, Frank J. Gonzalez, Kuan Minn Cha |
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| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty Aryl hydrocarbon receptor nuclear translocator medicine.medical_treatment lcsh:Medicine Blood sugar Biology Impaired glucose tolerance Mice Pregnancy Insulin-Secreting Cells Internal medicine Glucose Intolerance Insulin Secretion medicine Animals Cyclin D2 Insulin lcsh:Science Crosses Genetic Cell Proliferation Mice Knockout Multidisciplinary Aryl Hydrocarbon Receptor Nuclear Translocator lcsh:R Glucose-6-Phosphate Isomerase medicine.disease IRS2 Gestational diabetes Glucose Endocrinology Gene Expression Regulation Insulin Receptor Substrate Proteins Female lcsh:Q Beta cell Research Article |
| Zdroj: | PLoS ONE, Vol 8, Iss 10, p e77419 (2013) PLoS ONE |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0077419 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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