# Roles for Glucosensors in Taste Function

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2021 · $432,083

## Abstract

PROJECT SUMMARY
Obesity and diabetes are associated with the chronic overconsumption of high sugar foods and fluids, driven in
large part by their palatable taste. A single heterodimeric G-protein coupled receptor (T1R2+3) found in
mammalian taste cells is widely considered the principal means through which all simple sugars are detected
and promote ingestion via the gustatory system. Yet, recent studies from our laboratory revealed that rodents
come to respond more positively to the orosensory properties of glucose over fructose, when provided the
opportunity to learn about their divergent metabolic consequences, and this phenomenon does not require the
canonical T1R2+3 taste receptor. Collectively, these published studies point to the existence of a previously
unknown taste receptor linked to glucose appetite. The preliminary findings included in this proposal now show
that glucokinase, a phosphorylating enzyme involved in other glucosensing mechanisms, is expressed in murine
taste cells. We further demonstrate that glucokinase levels in the taste tissue are regulated by energy state and
dietary sugar exposure. Moreover, pharmacological activation of lingual glucokinase specifically bolsters licking
behavior and neural responsiveness in the chorda tympani nerve for glucose, but not fructose or water. Our
working hypothesis is that glucokinase is part of a T1R2+3-independent taste receptor that transduces glucose-
specific signals in the gustatory system. The overall goal of this proposal is to further clarify the functional and
molecular properties of this novel gustatory glucosensor. In Aim 1, we will combine genetic and pharmacological
approaches to selectively disrupt and/or activate canonical “sweet” taste inputs and lingual glucokinase while
measuring taste-driven licking for various “sweet” and “non-sweet” tastants in sugar-naïve and sugar-exposed
mice. With immunoblot and qPCR, we will further quantify changes in glucokinase and other sensory
mechanisms linked to glucokinase in taste tissue as a function of dietary sugar exposure. In Aim 2, we will
combine genetic and pharmacological approaches to psychophysically assess the discriminability of glucose,
fructose, and other tastants in a series of two response operant discrimination tasks in order to fully elucidate
the behavioral outputs functionally linked to gustatory glucosensors. In Aim 3, we will combine genetic and
pharmacological approaches with electrophysiology to determine how T1R2+3-independent, glucokinase-linked
taste signals are neurally-transmitted from tongue to brain. The outcomes of these aims will identify novel and
potentially critical aspects of nutrient sensing, with the ultimate goal of identifying potential new strategies to curb
appetite.

## Key facts

- **NIH application ID:** 10122702
- **Project number:** 1R01DC018562-01A1
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Lindsey A Schier
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $432,083
- **Award type:** 1
- **Project period:** 2020-12-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10122702

## Citation

> US National Institutes of Health, RePORTER application 10122702, Roles for Glucosensors in Taste Function (1R01DC018562-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10122702. Licensed CC0.

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