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Updated: Jun 3, 2025

High-resolution Respirometry to Measure Mitochondrial Function of Intact Beta Cells in the Presence of Natural Compounds
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High-resolution Respirometry to Measure Mitochondrial Function of Intact Beta Cells in the Presence of Natural Compounds

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Promotion of beta cell proliferation through DYRK kinase inhibition using the marine natural product breitfussin C

Sara Ullsten1, Kine Østnes Hansen1, Guillaume Axel Petit1

  • 1MARBIO, UiT - The Arctic University of Norway, Breivika, 9037, Tromsø, Norway.

Scientific Reports
|January 8, 2025
PubMed

Insights

Breitfussin C protects pancreatic beta cells from cytokine damage and promotes proliferation by inhibiting DYRK kinases. This natural compound shows potential for developing new diabetes therapies.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Marine Pharmacology

Background:

  • Pro-inflammatory cytokines induce pancreatic beta cell death and dysfunction, contributing to diabetes onset.
  • Targeting cytokine signaling pathways is a potential therapeutic strategy for diabetes.
  • Breitfussin C (BfC) is a natural compound from Thuiaria breitfussi with potential beta cell protective effects.

Purpose of the Study:

  • To investigate the protective and proliferative effects of breitfussin C (BfC) on pancreatic beta cells exposed to pro-inflammatory cytokines.
  • To explore the mechanism of BfC's action, including its effects on DYRK kinases and cell cycle regulation.

Main Methods:

  • Utilized the beta cell line RIN-M5F for experiments.
  • Assessed cell viability (MTS assay), apoptosis (caspase 3/7 activity), and proliferation (EdU incorporation, cell cycle distribution).
  • Investigated BfC's inhibition of DYRK kinases using biochemical assays, western blotting, and docking simulations.

Main Results:

  • BfC treatment significantly increased beta cell proliferation and counteracted cytokine-induced proliferation reduction.
  • BfC inhibited DYRK kinases, leading to decreased levels of the cell cycle inhibitor p27KIP.
  • BfC demonstrated a protective effect on beta cells against cytokine-induced damage.

Conclusions:

  • Breitfussin C promotes pancreatic beta cell proliferation via DYRK kinase inhibition.
  • BfC's mechanism involves downregulating the cell cycle inhibitor p27KIP.
  • BfC represents a potential therapeutic starting point for diabetes treatment by enhancing beta cell function and survival.
Keywords:
Beta cellsCytokinesDYRKDiabetesKinase inhibitionProliferation

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