GLP-1/GIP/GCG receptor triagonist (IUB447) enhances insulin secretion via GLP-1 receptor and Gαq signalling pathway in mice.
Quick Facts
What This Study Found
A triple-receptor agonist targeting GLP-1, GIP, and glucagon receptors boosted insulin secretion primarily through the GLP-1 receptor and the Gαq-TRPM5 signaling pathway in mouse islets. Removing this pathway eliminated the drug's blood sugar benefits in obese mice.
Key Numbers
IUB447 triagonist tested. Enhanced insulin secretion more than co-administered mono-agonists. Effect unchanged without GIP or glucagon receptors. Effect eliminated without both GLP-1R and GIPR, or with GLP-1R antagonist exendin-3(9-39). Gαq blocker YM254890 and TRPM5 blocker TPPO suppressed the effect. Trpm5 knockout mice showed no glycemic benefit.
How They Did This
Isolated islets from WT, Gipr-/-, Gcgr-/-, Glp1r/Gipr double-KO, and Trpm5-/- mice. Measured glucose-stimulated insulin secretion with triagonist vs mono-agonists. In vivo metabolic testing in WT and Trpm5-/- mice on chow and high-fat diets.
Why This Research Matters
Triple-receptor agonists are the next generation of obesity and diabetes drugs. Understanding that their insulin-boosting power comes mainly through GLP-1R and Gαq signaling helps guide future drug design.
What This Study Doesn't Tell Us
Mouse study only. Human islet signaling may differ. Single triagonist compound tested. In vivo results limited to one mouse strain and diet model.
Trust & Context
- Original Title:
- GLP-1/GIP/GCG receptor triagonist (IUB447) enhances insulin secretion via GLP-1 receptor and Gαq signalling pathway in mice.
- Published In:
- Diabetologia, 68(11), 2567-2580 (2025)
- Authors:
- Schreier, Pascale C F, Beyerle, Philipp, Boulassel, Severin, Beck, Andreas, Novikoff, Aaron, Reinach, Peter S, Boekhoff, Ingrid, Breit, Andreas, Neuberger, Arthur, Müller, Timo D, Serrano, Alberto Cebrian, Gudermann, Thomas, Khajavi, Noushafarin
- Database ID:
- RPEP-13473
Evidence Hierarchy
Read More on RethinkPeptides
Cite This Study
https://rethinkpeptides.com/research/RPEP-13473APA
Schreier, Pascale C F; Beyerle, Philipp; Boulassel, Severin; Beck, Andreas; Novikoff, Aaron; Reinach, Peter S; Boekhoff, Ingrid; Breit, Andreas; Neuberger, Arthur; Müller, Timo D; Serrano, Alberto Cebrian; Gudermann, Thomas; Khajavi, Noushafarin. (2025). GLP-1/GIP/GCG receptor triagonist (IUB447) enhances insulin secretion via GLP-1 receptor and Gαq signalling pathway in mice.. Diabetologia, 68(11), 2567-2580. https://doi.org/10.1007/s00125-025-06525-0
MLA
Schreier, Pascale C F, et al. "GLP-1/GIP/GCG receptor triagonist (IUB447) enhances insulin secretion via GLP-1 receptor and Gαq signalling pathway in mice.." Diabetologia, 2025. https://doi.org/10.1007/s00125-025-06525-0
RethinkPeptides
RethinkPeptides Research Database. "GLP-1/GIP/GCG receptor triagonist (IUB447) enhances insulin ..." RPEP-13473. Retrieved from https://rethinkpeptides.com/research/schreier-2025-glp1gipgcg-receptor-triagonist-iub447
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.