title: Glut4 expression defines an insulin-sensitive hypothalamic neuronal population.
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.
authors.affiliation: Department of Medicine and Berrie Diabetes Center, Columbia University College of Physicians & Surgeons, New York, NY 10032, USA.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Ren
authors.affiliation: Department of Pathology and Cell Biology, Columbia University College of Physicians & Surgeons, New York, NY 10032, USA.
authors.forename: Shijun
authors.initials: S
authors.lastname: Yan
authors.affiliation: Department of Medicine and Berrie Diabetes Center, Columbia University College of Physicians & Surgeons, New York, NY 10032, USA.
authors.forename: Baifang
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Medicine and Berrie Diabetes Center, Columbia University College of Physicians & Surgeons, New York, NY 10032, USA.
authors.forename: Taylor Y
authors.initials: TY
authors.lastname: Lu
authors.affiliation: Department of Pathology and Cell Biology, Columbia University College of Physicians & Surgeons, New York, NY 10032, USA.
authors.forename: Ottavio
authors.initials: O
authors.lastname: Arancio
authors.affiliation: Department of Medicine and Berrie Diabetes Center, Columbia University College of Physicians & Surgeons, New York, NY 10032, USA.
authors.forename: Domenico
authors.initials: D
authors.lastname: Accili
keywords: CNS; Glut4 neurons; Insulin signaling; Ion channel; Neurotransmitter receptor