Dynamic Ca2+-Dependent Transcription Links Metabolic Stress to Impaired β-Cell Identity
This study was undertaken to establish a temporal link between an increase in intracellular Ca2+ concentration and the loss of pancreatic β-cell identity. We profiled the alterations in Ca2+ dynamics and gene transcription that occur in freshly isolated islets following membrane depolarization. We show that initially adaptive Ca2+-dependent transcription changes, mediated largely by CREB and CREB-dependent transcription factors, rapidly become maladaptive, causing the loss of β-cell identity and function. We also show that many effector genes linked to nearby human type 2 diabetes susceptibility loci are regulated by Ca2+-dependent mechanisms.
Authors
- Matthew T. Dickerson (ORCID: https://orcid.org/0000-0002-6187-3951)
- Mark A. Magnuson (ORCID: https://orcid.org/0000-0002-8824-6499)
- David A. Jacobson (ORCID: https://orcid.org/0000-0003-1816-5375)
- Jean‐Philippe Cartailler (ORCID: https://orcid.org/0000-0002-0312-2391)
- Anna B. Osipovich (ORCID: https://orcid.org/0000-0002-9513-2262)
- Nicole M. Wright (ORCID: https://orcid.org/0000-0003-3235-0059)
- Shristi Shrestha (ORCID: https://orcid.org/0000-0003-4519-1712)
Institutions
- Vanderbilt University (US)
Publication Details
- Journal
- Diabetes
- Published
- 2025-06-17
- DOI
- https://doi.org/10.2337/db24-1141
- Citations
- 1
- Primary Topic
- Pancreatic function and diabetes
- Type
- article
- Field-Weighted Citation Impact
- 2.01
Funders
- Vanderbilt University
- National Institute of Diabetes and Digestive and Kidney Diseases