# Paracrine regulation of islet cell function by primary cilia

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2024 · $429,216

## Abstract

Project Summary/Abstract
The primary cilium plays critical roles in cellular signaling which within the pancreatic islets are
essential for the proper regulation of hormone secretion and blood glucose control. In both
humans and rodent models, diabetes manifests from misregulated islet cell secretory function
due to altered crosstalk and coordination among the key endocrine cells, but the etiology of islet
cell paracrine dysregulation in diabetes is unknown. Our recent studies reveal that primary cilia
are required for the maintenance of islet function by allowing islet cells to sense and respond to
each other’s activity status as communicated by hormonal cues. Based on these findings, we
hypothesize that primary cilia promote islet cell coordination by mediating paracrine hormone
signaling via the major α- and β-cell hormones. To these this hypothesis, we will use islet cell-
specific primary cilia deletion mouse models to delineate the mechanisms by which α/β-cell cilia
regulate paracrine hormone release and action on target cells. Aim 1 will determine whether
primary cilia mediate α-cell intra-islet signaling via glucagon and GLP-1. Aim 2 will determine
whether primary cilia mediate β-cell intra-islet signaling via insulin and serotonin. In both aims,
we will employ orthogonal imaging and biochemical approaches in primary islets to delineate a
physiologic role for primary cilia in islet function. A detailed understanding of islet cell inter-
regulation by primary cilia could support the development of novel therapies to treat or prevent
islet failure in diabetes.

## Key facts

- **NIH application ID:** 10854454
- **Project number:** 1R01DK138974-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Jing Wang Hughes
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $429,216
- **Award type:** 1
- **Project period:** 2024-05-01 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10854454

## Citation

> US National Institutes of Health, RePORTER application 10854454, Paracrine regulation of islet cell function by primary cilia (1R01DK138974-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10854454. Licensed CC0.

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