title: A Renal Olfactory Receptor Aids in Kidney Glucose Handling.
abstract: Olfactory receptors (ORs) are G protein-coupled receptors which serve important sensory functions beyond their role as odorant detectors in the olfactory epithelium. Here we describe a novel role for one of these ORs, Olfr1393, as a regulator of renal glucose handling. Olfr1393 is specifically expressed in the kidney proximal tubule, which is the site of renal glucose reabsorption. Olfr1393 knockout mice exhibit urinary glucose wasting and improved glucose tolerance, despite euglycemia and normal insulin levels. Consistent with this phenotype, Olfr1393 knockout mice have a significant decrease in luminal expression of Sglt1, a key renal glucose transporter, uncovering a novel regulatory pathway involving Olfr1393 and Sglt1. In addition, by utilizing a large scale screen of over 1400 chemicals we reveal the ligand profile of Olfr1393 for the first time, offering new insight into potential pathways of physiological regulation for this novel signaling pathway.
authors.affiliation: Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Blythe D
authors.initials: BD
authors.lastname: Shepard
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, CNRS, ERL 8228, Centre de Recherche des Cordeliers, Paris, France.
authors.forename: Lydie
authors.initials: L
authors.lastname: Cheval
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
authors.forename: Zita
authors.initials: Z
authors.lastname: Peterlin
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
authors.forename: Stuart
authors.initials: S
authors.lastname: Firestein
authors.affiliation: Department of Molecular Plant Physiology and Biophysics, Julius-von-Sachs-Institute, University Wurzburg, Julius-von-Sachs-Platz 2, 97082 Wurzburg, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Koepsell
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, CNRS, ERL 8228, Centre de Recherche des Cordeliers, Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Doucet
authors.affiliation: Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Pluznick
mesh_terms: D000818:Animals; D002460:Cell Line; D004285:Dogs; D005947:Glucose / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009831:Olfactory Mucosa / Q000378:metabolism; D018034:Olfactory Receptor Neurons / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D018035:Receptors, Odorant / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D051269:Sodium-Glucose Transporter 1 / Q000378:metabolism
chemical_list: D043562:Receptors, G-Protein-Coupled; D018035:Receptors, Odorant; D051269:Sodium-Glucose Transporter 1; D005947:Glucose