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Topics {✒️}

nature portfolio privacy policy author information authors policies advertising nature 442 nature na+-d-glucose cotransporter sglt2 na+-d-glucose cotransporter sglt1 0/ reprints modulating dynamin-dependent release gas chromatography-mass spectrometry structure-based drug design nih grants r00-dk081610 julius-von-sachs-institute julius-von-sachs-platz 2 amp-activated protein kinase hrp-conjugated secondary antibodies standard phenol-chloroform protocol flag-conjugated agarose beads dual-luciferase reporter assay free access na+/glucose cotransporter expression glucose/galactose malabsorption due evaluating cell-surface expression d-glucose cotransporter sglt1 protein-coupled odorant receptors cleavable lucy tag glucose-dependent incretin secretion full size image sglt-mediated glucose reabsorption account age-related decline middle overexpressing flag-tagged olfr1393 lucy-flag-olfr1393 construct widespread ectopic expression chemical library permissions ltl + tubule expressing sglt na-k-atpase activity neomycin selection marker sensory signaling systems urinary glucose-creatinine levels drug discovery mock rt-pcr reactions elevated protein/creatinine ratios dmem/f12 media johns hopkins chemcore luminal/total sglt stain fine-tune sglt1 regulation

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• How does your kidney smell?

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         description: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.
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