# Administrative Supplement: Roles for Glucosensors in Taste Function

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2023 · $368,662

## Abstract

PROJECT SUMMARY
 Diets high in sugar are significant risk factors for obesity, diabetes, and neurodegenerative diseases,
such as Alzheimer’s. The so called palatable “sweet” taste of these substances play a significant role in
promoting their appeal, sometimes at the expense of a balanced diet. In humans, AD progression is marked by
a decreased sensitivity to sweet taste, and increased cravings for more intensely sweet foods and fluids. While
it is commonly assumed these taste deficits result from impaired central nervous system function, the peripheral
conditions associated with the eventual onset of AD may also affect taste processing at its peripheral end organ,
the taste bud. In fact, very little is known about how the gustatory abnormalities develop, including if they emerge
early and contribute to AD progression. One aim of the parent R01 is to investigate how glucokinase, a
glucosensor intermediary, we found to be expressed in murine taste cells, contributes to the hedonic appeal of
sugar. To date, we showed that gustatory glucokinase is regulated by metabolic state and dietary sugar, and
contributes to the ability to detect glucose-containing sugars in the oral cavity. Although these processes do not
require the canonical sweet receptor (T1R2+T1R3), preliminary data included in this administrative supplement
now show that glucokinase activity affects sweet receptor expression in mice. Furthermore, in a set of pilot
studies, included here, we discovered significant alterations to the taste buds in a transgenic AD mouse model,
even in young adulthood. The 3xTg mouse has significantly smaller taste buds, which display high levels of the
inflammatory cytokine, TNFα, and less glucokinase, though further testing is needed. Precisely when these
morphological and molecular aberrations emerge, whether they are associated with concomitant sweet receptor
loss, and how they ultimately affect taste preferences remain unknown. Thus, the goal of this administrative
supplement is to extend Aim 1 of the parent R01 to investigate age-dependent changes in the taste bud
microenvironment and taste-guided behaviors in familial and sporadic AD. To do this, we will use
immunohistochemical techniques and rigorous behavioral taste testing to study two common transgenic mouse
lines, 3xTg and APOE4 knock in, which vary in their genetic predisposition to AD, across adulthood. The
outcomes of these aims will provide a better understanding of how gustatory glucosensing changes across the
lifespan and in response to the underlying metabolic-inflammatory conditions associated with AD. This
knowledge will be important for developing new strategies to assess AD symptoms and curb the excess sugar
intake exacerbating disease progression.

## Key facts

- **NIH application ID:** 10712541
- **Project number:** 3R01DC018562-03S2
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Lindsey A Schier
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $368,662
- **Award type:** 3
- **Project period:** 2020-12-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10712541

## Citation

> US National Institutes of Health, RePORTER application 10712541, Administrative Supplement: Roles for Glucosensors in Taste Function (3R01DC018562-03S2). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10712541. Licensed CC0.

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