Glut4 expression defines an insulin-sensitive hypothalamic neuronal population

Hongxia Ren, Shijun Yan, Baifang Zhang, Taylor Y. Lu, Ottavio Arancio, Domenico Accili

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Insulin signaling in the CNS modulates satiety and glucose metabolism, but insulin target neurons are poorly defined. We have previously shown that ablation of insulin receptors (InsR) in Glut4-expressing tissues results in systemic abnormalities of insulin action. We propose that Glut4 neurons constitute an insulin-sensitive neuronal subset. We determined their gene expression profiles using flow-sorted hypothalamic Glut4 neurons. Gene ontology analyses demonstrated that Glut4 neurons are enriched in olfacto-sensory receptors, M2 acetylcholine receptors, and pathways required for the acquisition of insulin sensitivity. Following genetic ablation of InsR, transcriptome profiling of Glut4 neurons demonstrated impairment of the insulin, peptide hormone, and cAMP signaling pathways, with a striking upregulation of anion homeostasis pathway. Accordingly, hypothalamic InsR-deficient Glut4 neurons showed reduced firing activity. The molecular signature of Glut4 neurons is consistent with a role for this neural population in the integration of olfacto-sensory cues with hormone signaling to regulate peripheral metabolism.

Original languageEnglish (US)
Pages (from-to)452-459
Number of pages8
JournalMolecular Metabolism
Volume3
Issue number4
DOIs
StatePublished - Jul 2014

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Keywords

  • CNS
  • Glut4 neurons
  • Insulin signaling
  • Ion channel
  • Neurotransmitter receptor

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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