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NOX4 signaling in pancreatic β-cells: Secrets hidden in the endoplasmic reticulum

Public support

  • Provider

    Czech Science Foundation

  • Programme

    Standard projects

  • Call for proposals

    SGA0202600001

  • Main participants

    Fyziologický ústav AV ČR, v. v. i.

  • Contest type

    VS - Public tender

  • Contract ID

    26-20384S

Alternative language

  • Project name in Czech

    NOX4 signaling in pancreatic β-cells: Secrets hidden in the endoplasmic reticulum

  • Annotation in Czech

    NADPH oxidase isoform 4 activity is key for redox signaling in pancreatic β-cells. Our data show that NOX4 deficiency impairs insulin secretion, increases proinsulin production, and promotes lipid accumulation under physiological conditions upon glucose stimulation. Preliminary findings indicate that glucose-induced NOX4-mediated redox signaling primarily targets the endoplasmic reticulum, with lipid accumulation probably arising as an adaptive response to ER stress caused by NOX4 loss. We propose to functionally validate the protein targets of NOX4-derived redox signaling and investigate how ER stress impacts lipid turnover, and derived post-translational modifications such as S-acylation directly targeting insulin secretion. This work aims to redefine NOX4's role in β-cell function by linking redox signaling with ER homeostasis, lipid metabolism, and insulin secretion. The findings are expected to provide critical insights into metabolic disease mechanisms and identify novel therapeutic strategies for preserving β-cell health.

Scientific branches

  • R&D category

    ZV - Basic research

  • OECD FORD - main branch

    10601 - Cell biology

  • OECD FORD - secondary branch

  • OECD FORD - another secondary branch

  • CEP - equivalent branches <br>(according to the <a href="http://www.vyzkum.cz/storage/att/E6EF7938F0E854BAE520AC119FB22E8D/Prevodnik_oboru_Frascati.pdf">converter</a>)

    EA - Morphology and cytology

Solution timeline

  • Realization period - beginning

    Jan 1, 2026

  • Realization period - end

    Dec 31, 2028

  • Project status

    Z - Beginning multi-year project

  • Latest support payment

Data delivery to CEP

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

  • Data delivery code

    CEP26-GA0-GA-R

  • Data delivery date

    Apr 27, 2026

Finance

  • Total approved costs

    12,448 thou. CZK

  • Public financial support

    12,326 thou. CZK

  • Other public sources

    122 thou. CZK

  • Non public and foreign sources

    0 thou. CZK