# Alternative Orosensory Signals Contributing to Sugar Taste

> **NIH NIH F31** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2023 · $41,294

## Abstract

PROJECT SUMMARY
The increase of obesity and diabetes in the US is associated with the highly palatable sugar content of the
western diet. The sweet taste receptor (T1R2+T1R3) is historically known to be the primary detector of sugars
and non-caloric sweeteners. However, recent investigations from my mentor demonstrated that mice with genetic
deletion of T1R2+T1R3 (or its downstream signaling mechanisms, TRPM5) still prefer the taste of glucose
and/maltose, suggesting the involvement of other orosensory receptors. The Schier lab recently identified a
glucose sensor in taste bud cells, glucokinase (GCK), that is upregulated with sugar exposure and is required to
rapidly detect and develop preference for glucose over fructose in sweet-sensitive mice. However, GCK does
not directly engage with maltose. Therefore I hypothesized that the α-glucosidase, maltase glucoamylase
(MGAM) generates free glucose ligands that activate nearby sweet receptors and/or GCK-linked sensors to drive
licking for maltose. My preliminary findings show that MGAM is upregulated in response to sugar exposure and
that virogenetic knockdown of either MGAM or GCK reduces the hedonic appeal of maltose in sweet-sensitive
mice. In this proposal, I aim to enhance this research by determining if MGAM- and GCK-linked behaviors
depend on TRPM5-mediated taste transduction (Aim 1). With additional training in fiber photometry, I further aim
to understand how the taste signals generated by metabolically distinct sugars recruit the mesolimbic
dopaminergic reward system to guide ingestive decisions (Aim 2). The overarching goal of these studies is to
understand and link glucosensing mechanisms to the central gustatory reward axis.

## Key facts

- **NIH application ID:** 10827641
- **Project number:** 1F31DC021376-01A1
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Aracely Simental-Ramos
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $41,294
- **Award type:** 1
- **Project period:** 2023-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10827641

## Citation

> US National Institutes of Health, RePORTER application 10827641, Alternative Orosensory Signals Contributing to Sugar Taste (1F31DC021376-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10827641. Licensed CC0.

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