# Metabolic signaling of the beta cell primary cilium

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2024 · $619,409

## Abstract

Project Summary
 Primary cilia serve as cellular sensors for rapid detection of environmental changes. These microtubule-
based antennae are expressed on almost all eukaryotic cells across unicellular and multicellular systems and
encompass wide roles in development and homeostasis. In recent years, primary cilia have come into the
limelight in diabetes and metabolism research, as previously unappreciated functions have been attributed to
these organelles on endocrine cells. Recent human genetic and GWAS studies show that cilia have clinically
important roles in metabolic diseases including obesity and diabetes. In the pancreatic islet, we observe that loss
of cilia disrupts β-cell endocrine functions including glucose-stimulated Ca2+ signaling and insulin secretion. Mice
lacking cilia on β-cells develop glucose intolerance and diet-induced diabetes. These findings suggest that
primary cilia mediate glucose responsiveness in normal β-cells, but the molecular drivers of ciliary glucose-
sensing and signaling are unknown. In addition, proteome and metabolome profiling have been done in other
mammalian cilia but not in pancreatic islet β-cells, posing a knowledge gap regarding cilia-dependent regulatory
mechanisms in β-cell glucose metabolism and secretory function. Our preliminary studies identify glycolytic
signaling machinery in β-cell cilia, both by proteomics and with a palette of newly developed biosensors that
monitor the dynamics of ciliary signaling. We further demonstrate that glycolytic fluxes differ between primary
cilia and cytosol in β-cells. Based on these findings, we hypothesize that compartmentalized glucose
metabolism in β-cell cilia generates signals that regulate ciliary and cellular function. To test this
hypothesis, we will combine genetic loss-of-function models with state-of-the-art proteomic and metabolic
profiling tools, microscopy, electrophysiological recordings, and islet function tests to delineate the mechanisms
by which cilia effect glucose-dependent β-cell functional changes. Aim 1 will leverage strong functional imaging,
proteomic, and metabolomics expertise and promising pilot data to delineate the signaling network by which
primary cilia relay glycolytic information and to comprehensively identify ciliary signaling pathways relevant to β-
cell function. Aim 2 will determine the mechanisms by which cilia regulate β-cell electrophysiological properties
and intracellular metabolic crosstalk leading to insulin secretion. A detailed understanding of these regulations
by primary cilia could support the development of novel therapies to modulate β-cell function in diabetes.

## Key facts

- **NIH application ID:** 10943580
- **Project number:** 1R01DK140365-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Jing Wang Hughes
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $619,409
- **Award type:** 1
- **Project period:** 2024-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10943580

## Citation

> US National Institutes of Health, RePORTER application 10943580, Metabolic signaling of the beta cell primary cilium (1R01DK140365-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10943580. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*