bioRxiv : the preprint server for biologyFeb 27, 2026

Primary cilia control GLP-1 signaling in insulin-producing pancreatic cells

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

Primary cilia appear to be required for GLP-1 receptor signaling that boosts insulin secretion in pancreatic β cells.

Evidence

This mouse and human islet experiment tested β-cell cilia loss, cAMP and Ca²⁺ responses, receptor localization, and Tulp3 knockdown effects on GLP-1-potentiated insulin secretion.

Caveat

The findings define a cellular signaling requirement in islet models, not clinical responses to GLP-1 receptor agonists in people.

Simplified

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are mainstay therapies for diabetes and obesity, acting in part by enhancing glucose-dependent insulin secretion. While the primary cilium is a known signaling compartment for certain G-protein coupled receptors (GPCRs), its role in the β-cell response to incretins remains undefined. Here, we show that primary cilia are essential for GLP-1R signaling. Loss of β-cell cilia in mouse and human islets severely impaired GLP-1-potentiated insulin secretion, an effect preceded by blunted whole-cell cAMP and Ca²⁺ responses. Immunofluorescence and immunogold scanning electron microscopy revealed endogenous GLP-1R localized to the primary cilium. Critically, disrupting ciliary GPCR trafficking via Tulp3 knockdown - while preserving cilia structure - recapitulated the signaling and secretory deficits, demonstrating a specific requirement for the ciliary receptor pool. These findings establish the primary cilium as a non-redundant signaling compartment for GLP-1R and uncover a new layer of subcellular organization in incretin action in β cells.

Full Text

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Primary cilia control GLP-1 signaling in insulin-producing pancreatic cells

Abstract

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