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
  • 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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