biostudies-literatureMiranda JGNIDDK NIH HHSJDRFNIH101430https://www.ebi.ac.uk/biostudies/studies/S-EPMC8804269biostudies-literatureUnknown57<h4>Objective</h4>Diabetes occurs because of insufficient insulin secretion due to β-cell dysfunction within the islet of Langerhans. Elevated glucose levels trigger β-cell membrane depolarization, action potential generation, and slow sustained free-Ca²⁺ ([Ca²⁺]) oscillations, which trigger insulin release. Nuclear factor of activated T-cell (NFAT) is a transcription factor, which is regulated by the increases in [Ca²⁺] and calceineurin (CaN) activation. NFAT regulation links cell activity with gene transcription in many systems and regulates proliferation and insulin granule biogenesis within the β-cell. However, the link between the regulation of β-cell electrical activity and oscillatory [Ca²⁺] dynamics with NFAT activation and downstream traMolecular metabolismDynamic changes in β-cell [Ca²⁺] regulate NFAT activation, gene transcription, and islet gap junction communication.PMC8804269F31 DK121488R01 DK106412P30 DK116073R01 DK102950R56 DK106412Miranda JGWells KLLandgrave SPRamirez DGSchleicher WEBenninger RKPfalseDynamic changes in β-cell [Ca²⁺] regulate NFAT activation, gene transcription, and islet gap junction communication.<h4>Objective</h4>Diabetes occurs because of insufficient insulin secretion due to β-cell dysfunction within the islet of Langerhans. Elevated glucose levels trigger β-cell membrane depolarization, action potential generation, and slow sustained free-Ca²⁺ ([Ca²⁺]) oscillations, which trigger insulin release. Nuclear factor of activated T-cell (NFAT) is a transcription factor, which is regulated by the increases in [Ca²⁺] and calceineurin (CaN) activation. NFAT regulation links cell activity with gene transcription in many systems and regulates proliferation and insulin granule biogenesis within the β-cell. However, the link between the regulation of β-cell electrical activity and oscillatory [Ca²⁺] dynamics with NFAT activation and downstream tra2022-01-01T00:00:00Z2022 Mar2025-04-04T19:53:58.218Z2025-04-04T19:53:58.218ZS-EPMC88042693497932910.1016/j.molmet.2021.101430