# Mechanisms of osmosensing in GI enteroendocrine cells

> **NIH NIH F30** · MAYO CLINIC ROCHESTER · 2024 · $49,174

## Abstract

PROJECT SUMMARY/ABSTRACT
The gastrointestinal (GI) epithelium directly senses components of foods we eat, which contain a variety of
nutritive and non-nutritive stimuli. These stimuli come from foods with a range of osmolality from zero (water) to
>1,500 mmol/kg-H2O for some of the saltiest foods. GI epithelial cells are not only first to sense luminal
osmoles, but these cells, along with the kidney tubular cells, encounter the largest osmole swings of all cells in
the body. In functional and motility GI disorders, such as irritable bowel syndrome (IBS), which affect 10 - 20%
of the US population, non-nutritive aspects of diets such as osmolality are often first line therapies. For
example, FODMAPs (Fermentable Oligo-, Di-, Monosaccharides and Polyols) are targeted for elimination in
IBS diets. FODMAPs are also highly osmotically active – they are known to drive luminal volume shifts which
may lead to symptoms. Both hypo- and hyper-osmotic stimuli invoke downstream signaling that regulates GI
motility and systemic physiologic responses. The enteroendocrine cells (EECs) are specialized sensory
epithelial cells that interact with luminal stimuli, both nutritive and non-nutritive, and these cells are capable of
regulating both local and systemic physiology including GI motility. While EECs are traditionally considered to
be nutrient sensors, our lab discovered an EEC subpopulation that transduces mechanical signals, thereby
opening the door to EECs being sensors of non-nutritive stimuli. Literature has shown that EEC receptor
activation drives two main signal transduction pathways: calcium (Ca2+) and cAMP which lead to release of a
range of signaling molecules, including serotonin (5HT). To investigate how EECs sense hyper and
hypoosmotic stimuli respectively, our lab is manipulating EEC receptors: V1aR, VRAC, and Piezo2. In VRAC
proteins, Ca2+ signaling drives Cl- currents. Understanding osmo-transduction will provide mechanistic insights
into commonly used clinical therapies. The overall goal of this proposal is to uncover the mechanisms by which
osmolality is sensed by EECs and how osmotic stimuli may engage EEC signal transduction to alter release of
signaling molecules and systemic GI physiology. The hypothesis is that EECs transduce osmotic stimuli in
location and subtype-specific ways - via cytoplasmic Ca2+, Cl- and cAMP, through osmoregulatory proteins,
and secrete signaling molecules to modulate GI motility. Aim 1 investigates the cellular pathways by which
EECs transduce osmotic stimuli. Aim 2 investigates the osmotically induced extracellular release of signaling
molecules by EECs and subsequent changes in GI motility. The results of this work are poised to bridge
knowledge gaps in EEC osmo-transduction, as well as inform broader osmosensing mechanisms in sensory
epithelia. The proposed work will be carried out in an environment that provides expert knowledge towards
achieving the specified goal, including collaborations with experts in v...

## Key facts

- **NIH application ID:** 10994977
- **Project number:** 1F30DK138638-01A1
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Shreya Bellampalli
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $49,174
- **Award type:** 1
- **Project period:** 2024-09-01 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10994977

## Citation

> US National Institutes of Health, RePORTER application 10994977, Mechanisms of osmosensing in GI enteroendocrine cells (1F30DK138638-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10994977. Licensed CC0.

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