A Renal Olfactory Receptor Aids in Kidney Glucose Handling

Sci Rep. 2016 Oct 14;6:35215. doi: 10.1038/srep35215.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Dogs
  • Glucose / metabolism*
  • HEK293 Cells
  • Humans
  • Kidney Tubules, Proximal / metabolism*
  • Madin Darby Canine Kidney Cells
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Olfactory Mucosa / metabolism
  • Olfactory Receptor Neurons / metabolism*
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, Odorant / metabolism
  • Signal Transduction / physiology
  • Sodium-Glucose Transporter 1 / metabolism

Substances

  • Receptors, G-Protein-Coupled
  • Receptors, Odorant
  • Sodium-Glucose Transporter 1
  • Glucose