Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
microRNA-205-5p is a modulator of insulin sensitivity that inhibits FOXO function
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Stockholm University, Science for Life Laboratory (SciLifeLab).
Show others and affiliations
Number of Authors: 72018 (English)In: Molecular metabolism, ISSN 2212-8778, Vol. 17, p. 49-60Article in journal (Refereed) Published
Abstract [en]

Objectives: Hepatic insulin resistance is a hallmark of type 2 diabetes and obesity. Insulin receptor signaling through AKT and FOXO has important metabolic effects that have traditionally been ascribed to regulation of gene expression. However, whether all the metabolic effects of FOXO arise from its regulation of protein-encoding mRNAs is unknown. Methods: To address this question, we obtained expression profiles of FOXO-regulated murine hepatic microRNAs (miRNAs) during fasting and refeeding using mice lacking Foxo1, 3a, and 4 in liver (L-Foxo1,3a, 4). Results: Out of 439 miRNA analyzed, 175 were differentially expressed in Foxo knockouts. Their functions were associated with insulin, Wnt, Mapk signaling, and aging. Among them, we report a striking increase of miR-205-5p expression in L-Foxo1,3a,4 knockouts, as well as in obese mice. We show that miR-205-5p gain-of-function increases AKT phosphorylation and decreases SHIP2 in primary hepatocytes, resulting in FOXO inhibition. This results in decreased hepatocyte glucose production. Consistent with these observations, miR-205-5p gain-of-function in mice lowered glucose levels and improved pyruvate tolerance. Conclusions: These findings reveal a homeostatic miRNA loop regulating insulin signaling, with potential implications for in vivo glucose metabolism.

Place, publisher, year, edition, pages
2018. Vol. 17, p. 49-60
Keywords [en]
Insulin resistance, Type 2 diabetes, Transcriptional regulation, Liver metabolism, Glucose production, Genetics
National Category
Biological Sciences Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:su:diva-162108DOI: 10.1016/j.molmet.2018.08.003ISI: 000447687500005PubMedID: 30174230OAI: oai:DiVA.org:su-162108DiVA, id: diva2:1263352
Available from: 2018-11-15 Created: 2018-11-15 Last updated: 2020-03-05Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Tarbier, MarcelCamastra, StefaniaFriedländer, Marc R.
By organisation
Department of Molecular Biosciences, The Wenner-Gren InstituteScience for Life Laboratory (SciLifeLab)
Biological SciencesEndocrinology and Diabetes

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 46 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf