Essay On Dna Methylation - 1075 Words

In this study, we describe DNA methylation and gene expression of SLC22A1, SLC22A3, and SLC47A1, which respectively encode the three metformin transporters OCT1, OCT3, and MATE1, in the human liver. In agreement with a previous study where OCT1 was found to be the most expressed drug transporter in the liver [15], we found higher mRNA expression of SLC22A1 than SLC22A3 (Additional file 1: Figure S2A). SLC47A1 was also highly expressed in the liver, as previously reported [16]. Metformin transporter genes have been studied in vivo in rodents to explain metformin pharmacodynamics. The distribution of metformin to the liver in Oct1 −/− mice was reduced 30-fold compared with wild-type mice [6], and the glucose-lowering effects of metformin†¦show more content†¦The fact that methylation of some studied CpG sites was not affected by the exposure in vitro does not exclude that longer metformin or insulin treatments could have effects. T2D patients are given a long-term therapy, whereas the cells were treated for 8 h mimicking an acute therapy. Overall, our in vivo and in vitro data support that metformin therapy is associated with lower DNA methylation of metformin transporter genes in the liver suggesting that epigenetics could be a potential mechanism for metformin action in the human liver. Accordingly, a recent study has shown that metformin alters DNA methylation in endometrial cancer cells [22]. The demethylation process in metformin tr ansporters induced by metformin could have occurred passively or actively by ten-eleven translocation (TET) enzymes [23], since these enzymes play an important role in the development and function of the human liver [24]. Moreover, AMPK pathway, activated by metformin, elevates ÃŽ ±-ketoglutarate metabolite which is required by TET catalytic reaction for the DNA demethylation process [25]. Nevertheless, more studies are needed to dissect this mechanism. In addition, diabetics who were only on metformin therapy had a similar or lower degree of methylation in these metformin transporter genes compared to non-diabetic people, suggesting a possibleShow MoreRelatedA Study Of Changes Throughout Gene Expression1567 Words   |  7 Pagesbe inherited with no changes to the DNA sequence itself- it may account for non-Mendelian population inheritance patterns. Transgenerational inheritance requires a chromosomal or epigenetic change in the germline allowing the information to be passed on fro m one generation to another (Anway et al 2005a). In order for epigenetic marks to be passed down, the gametes need to conserve their epigenomes by avoiding two reprogramming events; in the gamete and zygote. 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