RAMP3 Enhances GLP-1-Mediated Insulin Secretion (Preprint) | Research

The takeaway

This preprint (later published in JBC) shows RAMP3 modifies GLP-1 receptor signaling to enhance insulin secretion, suggesting a path to tissue-selective GLP-1 drugs.

Preprint of peer-reviewed finding
This bioRxiv preprint was subsequently published in the Journal of Biological Chemistry, confirming RAMP3 modification of GLP-1 signaling

What the researchers found

RAMP3 interacts with the GLP-1 receptor, modifying its signaling profile and enhancing insulin secretion — findings later confirmed in the peer-reviewed publication.

Why it matters

Demonstrates that receptor accessory proteins can modify GLP-1 signaling in ways that could lead to safer, more targeted diabetes drugs.

The numbers in context

Same as RPEP-12215.

How the study worked

Cell-based laboratory study examining RAMP3-GLP-1 receptor interaction, signaling bias, and functional effects on insulin secretion (preprint version).

Who was studied

Not applicable (cell-based study)

What this study cannot tell us

Preprint version — not yet peer-reviewed at time of posting. The peer-reviewed version was subsequently published in JBC (PMID 40835007).

How to read the evidence

Preprint version of a study later peer-reviewed and published. The peer-reviewed version (PMID 40835007) represents the definitive record.

When this study was published

Posted as preprint in 2025, with the peer-reviewed version published in the Journal of Biological Chemistry the same year.

The bigger picture

RAMPs could be the key to developing next-generation incretin drugs with improved tissue selectivity and reduced off-target effects.

Questions still open

How does the final published version differ from this preprint?
Can RAMP3-biased GLP-1 agonists be developed for clinical testing?

Common questions

Is this the same study as PMID 40835007?

Yes. This is the bioRxiv preprint version of the same research, which was subsequently peer-reviewed and published in the Journal of Biological Chemistry.

What did this study find about RAMP3 and GLP-1?

RAMP3 physically pairs with the GLP-1 receptor and shifts its signaling toward calcium pathways, enhancing insulin secretion. This could enable development of GLP-1 drugs that target specific tissues with fewer side effects.

Read the original research

Receptor Activity-Modifying Protein 3 enhances GLP-1-mediated Insulin Secretion.

bioRxiv : the preprint server for biology

View on PubMed ↗Publisher’s paper ↗

Citation

Pearce, Abigail; Kumari, Poonam; Sisk, Claudia M; Harris, Matthew; Yeung, Ho Yan; Winfield, Sabrina; Caron, Kathleen M; Ladds, Graham. (2025). Receptor Activity-Modifying Protein 3 enhances GLP-1-mediated Insulin Secretion.. bioRxiv : the preprint server for biology. https://doi.org/10.1101/2025.01.24.634724