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• W2955660432 abstract "MicroRNAs (miRNAs) are important posttranscriptional regulators of metabolism and energy homeostasis. Dysregulation of certain miRNAs in the liver has been shown to contribute to the pathogenesis of Type 2 diabetes (T2D), in part by impairing hepatic insulin sensitivity. By small RNA-sequencing analysis, we identified seven hepatic miRNAs (including miR-29b) that are consistently aberrantly expressed across five different rodent models of metabolic dysfunction that share the feature of insulin resistance (IR). We also showed that hepatic miR-29b exhibits persistent dysregulation during disease progression in a rat model of diabetes, UCD-T2DM. Furthermore, we observed that hepatic levels of miR-29 family members are attenuated by interventions known to improve IR in rodent and rhesus macaque models. To examine the function of the miR-29 family in modulating insulin sensitivity, we used locked nucleic acid (LNA) technology and demonstrated that acute in vivo suppression of the miR-29 family in adult mice leads to significant reduction of fasting blood glucose (in both chow-fed lean and high-fat diet-fed obese mice) and improvement in insulin sensitivity (in chow-fed lean mice). We carried out whole transcriptome studies and uncovered candidate mechanisms, including regulation of DNA methyltransferase 3a ( Dnmt3a) and the hormone-encoding gene Energy homeostasis associated ( Enho). In sum, we showed that IR/T2D is linked to dysregulation of hepatic miR-29b across numerous models and that acute suppression of the miR-29 family in adult mice leads to improved glycemic control. Future studies should investigate the therapeutic utility of miR-29 suppression in different metabolic disease states. Enho; insulin resistance; liver; microRNA-29 (miR-29); UCD-T2DM" @default.
• W2955660432 created "2019-07-12" @default.
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• W2955660432 date "2019-08-01" @default.
• W2955660432 modified "2023-10-13" @default.
• W2955660432 title "Acute suppression of insulin resistance-associated hepatic miR-29 in vivo improves glycemic control in adult mice" @default.
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• W2955660432 doi "https://doi.org/10.1152/physiolgenomics.00037.2019" @default.
• W2955660432 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6732414" @default.
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