# Elucidating the Role of Olfactory Receptor 1393 in Renal Glucose Handling

> **NIH NIH K01** · GEORGETOWN UNIVERSITY · 2020 · $127,727

## Abstract

Project Summary
Olfactory receptors (ORs) are seven transmembrane domain G protein-coupled chemosensory receptors that
serve as sensors of smell in the nose. Recently, studies have found that ORs and other chemosensors are
also expressed outside of their native tissues, including in sperm, muscle and the spinal column, where they
have important functional roles. We have previously reported that OR signaling also plays a role in the kidney
and recently found one of these receptors, Olfr1393, to be found on the apical plasma membrane of the
proximal tubule. Olfr1393 knockout (KO) mice present with euglycemic glycosuria and improved glucose
tolerance. Thus, it appears that Olfr1393 plays a role in renal glucose handling. Glucose is freely filtered by
the renal glomerulus, and nearly 100% of it is reabsorbed from the lumen of the proximal tubule by two
sodium-glucose co-transporters, Sglt1 and Sglt2. These transporters handle all glucose reabsorption, and it is
typically only during periods of hyperglycemia that glucose appears in the urine. In keeping with a function for
Olfr1393 in glucose handling, we found that there is a 22% decrease in the luminal staining of Sglt1 in Olfr1393
KO mice, but no change in Sglt2. Thus, we propose that Olfr1393 is a novel regulator for Sglt1 in the renal
proximal tubule. In this proposal, we are aiming to understand how Olfr1393 regulates Sglt1 by examining its
ability to influence Sglt1 localization, expression or activity. In addition, we will examine Olfr1393 in the context
of the only other known basal regulator of Sglt1, RS1. Finally, we are also investigating how Olfr1393 signaling
functions in the progression of diabetes, and whether modulation can lower plasma glucose. To do that, we
will induce diabetes in Olfr1393 wild type and KO mice and investigate their rise in plasma glucose, glucose
tolerance, glomerular filtration rate and progression of neuropathy and vascular disease. The candidate's
goals are to understand renal physiology and renal transporter regulation, and this proposal will be completed
under the guidance of an experienced mentor team that includes accomplished renal physiologists and
metabolic researchers. To accomplish this, the candidate will work with her mentors and the Professional
Development Office to follow a career development plan that includes manuscript preparation, attending and
presenting at international conferences and departmental seminars, mentoring of graduate and undergraduate
students, and preparation of application materials.

## Key facts

- **NIH application ID:** 9933904
- **Project number:** 5K01DK106400-05
- **Recipient organization:** GEORGETOWN UNIVERSITY
- **Principal Investigator:** Blythe D Shepard
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $127,727
- **Award type:** 5
- **Project period:** 2016-08-29 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9933904

## Citation

> US National Institutes of Health, RePORTER application 9933904, Elucidating the Role of Olfactory Receptor 1393 in Renal Glucose Handling (5K01DK106400-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9933904. Licensed CC0.

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