2. Academic Validation
  3. Dynamic Ca2+-Dependent Transcription Links Metabolic Stress to Impaired β-Cell Identity

Dynamic Ca2+-Dependent Transcription Links Metabolic Stress to Impaired β-Cell Identity

  • Diabetes. 2025 Jun 17:db241141. doi: 10.2337/db24-1141.
Anna B Osipovich 1 2,  Matthew T Dickerson 1,  Jean-Philippe Cartailler 2,  Shristi Shrestha 2,  Nicole M Wright 3,  David A Jacobson 1,  Mark A Magnuson 1 2 4
Affiliations

Affiliations

  • 1 Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN.
  • 2 Center for Stem Cell Biology, Vanderbilt University, Nashville, TN.
  • 3 College of Arts and Sciences, Vanderbilt University, Nashville, TN.
  • 4 Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN.
PMID: 40526459 DOI: 10.2337/db24-1141
Abstract

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.

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