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- Reusens, B., et al.
(författare)
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The intrauterine metabolic environment modulates the gene expression pattern in fetal rat islets: prevention by maternal taurine supplementation
- 2008
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 51:5, s. 836-845
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis Events during fetal life may in critical time windows programme tissue development leading to organ dysfunction with potentially harmful consequences in adulthood such as diabetes. In rats, the beta cell mass of progeny from dams fed with a low-protein (LP) diet during gestation is decreased at birth and metabolic perturbation lasts through adulthood even though a normal diet is given after birth or after weaning. Maternal and fetal plasma taurine levels are suboptimal. Maternal taurine supplementation prevents these induced abnormalities. In this study, we aimed to reveal changes in gene expression in fetal islets affected by the LP diet and how taurine may prevent these changes. Methods Pregnant Wistar rats were fed an LP diet (8% [wt/wt] protein) supplemented or not with taurine in the drinking water or a control diet (20% [wt/wt] protein). At 21.5 days of gestation, fetal pancreases were removed, digested and cultured for 7 days. Neoformed islets were collected and transcriptome analysis was performed. Results Maternal LP diet significantly changed the expression of more than 10% of the genes. Tricarboxylic acid cycle and ATP production were highly targeted, but so too were cell proliferation and defence. Maternal taurine supplementation normalised the expression of all altered genes. Conclusions/Interpretation Development of the beta cells and particularly their respiration is modulated by the intrauterine environment, which may epigenetically modify expression of the genome and programme the beta cell towards a pre-diabetic phenotype. This mis-programming by maternal LP diet was prevented by early taurine intervention.
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| 2. |
- Bergholdt, R, et al.
(författare)
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Transcriptional profiling of type 1 diabetes genes on chromosome 21 in a rat beta-cell line and human pancreatic islets
- 2007
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Ingår i: Genes and Immunity. - : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 8:3, s. 232-238
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Tidskriftsartikel (refereegranskat)abstract
- We recently finemapped a type 1 diabetes (T1D)-linked region on chromosome 21, indicating that one or more T1D-linked genes exist in this region with 33 annotated genes. In the current study, we have taken a novel approach using transcriptional profiling in predicting and prioritizing the most likely candidate genes influencing beta-cell function in this region. Two array-based approaches were used, a rat insulinoma cell line (INS-1 alpha beta) overexpressing pancreatic duodenum homeobox 1 (pdx-1) and treated with interleukin 1 beta (IL-1 beta) as well as human pancreatic islets stimulated with a mixture of cytokines. Several candidate genes with likely functional significance in T1D were identified. Genes showing differential expression in the two approaches were highly similar, supporting the role of these specific gene products in cytokine-induced beta-cell damage. These were genes involved in cytokine signaling, oxidative phosphorylation, defense responses and apoptosis. The analyses, furthermore, revealed several transcription factor binding sites shared by the differentially expressed genes and by genes demonstrating highly similar expression profiles with these genes. Comparable findings in the rat beta-cell line and human islets support the validity of the methods used and support this as a valuable approach for gene mapping and identification of genes with potential functional significance in T1D, within a region of linkage.
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