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Acute suppression of insulin resistance-associated hepatic miR-29 in vivo improves glycemic control in adult mice.

Publication ,  Journal Article
Hung, Y-H; Kanke, M; Kurtz, CL; Cubitt, R; Bunaciu, RP; Miao, J; Zhou, L; Graham, JL; Hussain, MM; Havel, P; Biddinger, S; White, PJ; Sethupathy, P
Published in: Physiol Genomics
August 1, 2019

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.

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Published In

Physiol Genomics

DOI

EISSN

1531-2267

Publication Date

August 1, 2019

Volume

51

Issue

8

Start / End Page

379 / 389

Location

United States

Related Subject Headings

  • Rats, Zucker
  • Rats
  • Oligonucleotides
  • MicroRNAs
  • Mice, Obese
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Macaca mulatta
  • Liver
 

Citation

APA
Chicago
ICMJE
MLA
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Hung, Y.-H., Kanke, M., Kurtz, C. L., Cubitt, R., Bunaciu, R. P., Miao, J., … Sethupathy, P. (2019). Acute suppression of insulin resistance-associated hepatic miR-29 in vivo improves glycemic control in adult mice. Physiol Genomics, 51(8), 379–389. https://doi.org/10.1152/physiolgenomics.00037.2019
Hung, Yu-Han, Matt Kanke, C Lisa Kurtz, Rebecca Cubitt, Rodica P. Bunaciu, Ji Miao, Liye Zhou, et al. “Acute suppression of insulin resistance-associated hepatic miR-29 in vivo improves glycemic control in adult mice.Physiol Genomics 51, no. 8 (August 1, 2019): 379–89. https://doi.org/10.1152/physiolgenomics.00037.2019.
Hung Y-H, Kanke M, Kurtz CL, Cubitt R, Bunaciu RP, Miao J, et al. Acute suppression of insulin resistance-associated hepatic miR-29 in vivo improves glycemic control in adult mice. Physiol Genomics. 2019 Aug 1;51(8):379–89.
Hung, Yu-Han, et al. “Acute suppression of insulin resistance-associated hepatic miR-29 in vivo improves glycemic control in adult mice.Physiol Genomics, vol. 51, no. 8, Aug. 2019, pp. 379–89. Pubmed, doi:10.1152/physiolgenomics.00037.2019.
Hung Y-H, Kanke M, Kurtz CL, Cubitt R, Bunaciu RP, Miao J, Zhou L, Graham JL, Hussain MM, Havel P, Biddinger S, White PJ, Sethupathy P. Acute suppression of insulin resistance-associated hepatic miR-29 in vivo improves glycemic control in adult mice. Physiol Genomics. 2019 Aug 1;51(8):379–389.

Published In

Physiol Genomics

DOI

EISSN

1531-2267

Publication Date

August 1, 2019

Volume

51

Issue

8

Start / End Page

379 / 389

Location

United States

Related Subject Headings

  • Rats, Zucker
  • Rats
  • Oligonucleotides
  • MicroRNAs
  • Mice, Obese
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Macaca mulatta
  • Liver