دورية أكاديمية
Differential DNA Methylation and Expression of miRNAs in Adipose Tissue From Twin Pairs Discordant for Type 2 Diabetes.
| العنوان: | Differential DNA Methylation and Expression of miRNAs in Adipose Tissue From Twin Pairs Discordant for Type 2 Diabetes. |
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| المؤلفون: | Nilsson E; Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Scania University Hospital, Malmö, Sweden emma_a.nilsson@med.lu.se., Vavakova M; Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Scania University Hospital, Malmö, Sweden.; Diabetes, Metabolism and Endocrinology, Department of Experimental Medical Science, Lund University, Lund, Sweden., Perfilyev A; Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Scania University Hospital, Malmö, Sweden., Säll J; Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Scania University Hospital, Malmö, Sweden., Jansson PA; Wallenberg Laboratory, Sahlgrenska University Hospital, Gothenburg, Sweden., Poulsen P; Global Development, Novo Nordisk A/S, Søborg, Denmark., Esguerra JLS; Islet Cell Exocytosis Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Malmö, Sweden., Eliasson L; Islet Cell Exocytosis Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Malmö, Sweden., Vaag A; Steno Diabetes Center Copenhagen, Gentofte, Denmark., Göransson O; Diabetes, Metabolism and Endocrinology, Department of Experimental Medical Science, Lund University, Lund, Sweden., Ling C; Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Scania University Hospital, Malmö, Sweden. |
| المصدر: | Diabetes [Diabetes] 2021 Oct; Vol. 70 (10), pp. 2402-2418. Date of Electronic Publication: 2021 Jul 27. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Twin Study |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Diabetes Association Country of Publication: United States NLM ID: 0372763 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1939-327X (Electronic) Linking ISSN: 00121797 NLM ISO Abbreviation: Diabetes Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Alexandria, VA : American Diabetes Association Original Publication: [New York, American Diabetes Association] |
| مواضيع طبية MeSH: | Twins, Monozygotic*/genetics, Adipose Tissue/*metabolism , Diabetes Mellitus, Type 2/*genetics , MicroRNAs/*genetics, 3T3-L1 Cells ; Adipose Tissue/pathology ; Aged ; Animals ; Arrhythmias, Cardiac/genetics ; Arrhythmias, Cardiac/pathology ; Case-Control Studies ; Cells, Cultured ; Cohort Studies ; DNA Methylation ; Denmark ; Diabetes Mellitus, Type 2/metabolism ; Diabetes Mellitus, Type 2/pathology ; Diseases in Twins/genetics ; Female ; Gene Expression ; Genetic Diseases, X-Linked/genetics ; Genetic Diseases, X-Linked/pathology ; Gigantism/genetics ; Gigantism/pathology ; Heart Defects, Congenital/genetics ; Heart Defects, Congenital/pathology ; Humans ; Intellectual Disability/genetics ; Intellectual Disability/pathology ; Male ; Mice ; MicroRNAs/metabolism ; Middle Aged ; Sweden |
| مستخلص: | The prevalence of type 2 diabetes (T2D) is increasing worldwide, but current treatments have limitations. miRNAs may play a key role in the development of T2D and can be targets for novel therapies. Here, we examined whether T2D is associated with altered expression and DNA methylation of miRNAs using adipose tissue from 14 monozygotic twin pairs discordant for T2D. Four members each of the miR-30 and let-7-families were downregulated in adipose tissue of subjects with T2D versus control subjects, which was confirmed in an independent T2D case-control cohort. Further, DNA methylation of five CpG sites annotated to gene promoters of differentially expressed miRNAs, including miR-30a and let-7a-3, was increased in T2D versus control subjects. Luciferase experiments showed that increased DNA methylation of the miR-30a promoter reduced its transcription in vitro. Silencing of miR-30 in adipocytes resulted in reduced glucose uptake and TBC1D4 phosphorylation; downregulation of genes involved in demethylation and carbohydrate/lipid/amino acid metabolism; and upregulation of immune system genes. In conclusion, T2D is associated with differential DNA methylation and expression of miRNAs in adipose tissue. Downregulation of the miR-30 family may lead to reduced glucose uptake and altered expression of key genes associated with T2D. (© 2021 by the American Diabetes Association.) |
| سلسلة جزيئية: | figshare 10.2337/figshare.15036348 |
| المشرفين على المادة: | 0 (MicroRNAs) |
| SCR Disease Name: | Simpson-Golabi-Behmel syndrome |
| تواريخ الأحداث: | Date Created: 20210728 Date Completed: 20211221 Latest Revision: 20211221 |
| رمز التحديث: | 20240829 |
| DOI: | 10.2337/db20-0324 |
| PMID: | 34315727 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1939-327X |
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| DOI: | 10.2337/db20-0324 |