Liraglutide Treatment Reverses Unconventional Cellular Defects in Induced Pluripotent Stem Cell–Derived β-Cells Harboring a Partially Functional <i>WFS1</i> Variant

The molecular basis of WFS1-related mutations remains poorly investigated, and no definitive therapies exist for Wolfram syndrome 1. We dissected the molecular defects associated with c.316-1G>A and c.757A>T WFS1 mutations in patient-derived induced pluripotent stem cell islets and analyzed whether they are potential therapeutic targets of the glucagon-like peptide 1 receptor agonist liraglutide. We found impaired insulin granule maturation, altered Ca2+ fluxes, increased autophagic activity, and heightened susceptibility to inflammatory apoptosis in mutated cells. Liraglutide restored critical β-cell functions suggesting a route for personalized therapy based on WFS1 mutations.

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Journal
Diabetes
Published
2025-04-09
DOI
https://doi.org/10.2337/db24-0720
Citations
3
Primary Topic
Pancreatic function and diabetes
Type
article
Field-Weighted Citation Impact
6.02
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article

Liraglutide Treatment Reverses Unconventional Cellular Defects in Induced Pluripotent Stem Cell–Derived β-Cells Harboring a Partially Functional WFS1 Variant

Lorenzo Piemonti, Gabriel Siracusano, Valeria Sordi, Federica Cuozzo et al.
3 citations
Diabetes
Pancreatic function and diabetes
6.02
article

Liraglutide Treatment Reverses Unconventional Cellular Defects in Induced Pluripotent Stem Cell–Derived β-Cells Harboring a Partially Functional WFS1 Variant

Lorenzo Piemonti, Gabriel Siracusano, Valeria Sordi, Federica Cuozzo, Raniero Chimienti, Silvia Pellegrini, Fabio Manenti, S. Torchio, Riccardo Bonfanti, Valentina Zamarian, Giulio Frontino
article en
3 citations

Abstract

The molecular basis of WFS1-related mutations remains poorly investigated, and no definitive therapies exist for Wolfram syndrome 1. We dissected the molecular defects associated with c.316-1G>A and c.757A>T WFS1 mutations in patient-derived induced pluripotent stem cell islets and analyzed whether they are potential therapeutic targets of the glucagon-like peptide 1 receptor agonist liraglutide. We found impaired insulin granule maturation, altered Ca2+ fluxes, increased autophagic activity, and heightened susceptibility to inflammatory apoptosis in mutated cells. Liraglutide restored critical β-cell functions suggesting a route for personalized therapy based on WFS1 mutations.

DiabetesVol. 74(7)
Vita-Salute San Raffaele University (IT), San Raffaele University of Rome (IT), IRCCS Ospedale San Raffaele (IT), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele (IT)
No poverty
Openalex Percentile: Top 4%
Pancreatic function and diabetes
6.02
DOIOpen Access PDFOpenAlex
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Liraglutide Treatment Reverses Unconventional Cellular Defects in Induced Pluripotent Stem Cell–Derived β-Cells Harboring a Partially Functional <i>WFS1</i> Variant — Lorenzo Piemonti, Gabriel Siracusano, et al. · Diabetes (2025) | TGRS Research Map | TGRS