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Beyond glucose: The crucial role of redox signaling in ß-cell metabolic adaptation.
Holendová, Blanka; Salovská, Barbora; Benáková, Stepánka; Plecitá-Hlavatá, Lydie.
Afiliación
  • Holendová B; Laboratory of Pancreatic Islet Research, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic. Electronic address: blanka.holendova@fgu.cas.cz.
  • Salovská B; Department of Genome Integrity, Institute of Molecular Genetics, Czech Academy of Sciences, Prague, Czech Republic; Yale Cancer Biology Institute, Yale University School of Medicine, West Haven, CT, USA.
  • Benáková S; Laboratory of Pancreatic Islet Research, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic; First Faculty of Medicine, Charles University, Prague, Czech Republic.
  • Plecitá-Hlavatá L; Laboratory of Pancreatic Islet Research, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic. Electronic address: lydie.plecita@fgu.cas.cz.
Metabolism ; : 156027, 2024 Sep 09.
Article en En | MEDLINE | ID: mdl-39260557
ABSTRACT

OBJECTIVE:

Redox signaling mediated by reversible oxidative cysteine thiol modifications is crucial for driving cellular adaptation to dynamic environmental changes, maintaining homeostasis, and ensuring proper function. This is particularly critical in pancreatic ß-cells, which are highly metabolically active and play a specialized role in whole organism glucose homeostasis. Glucose stimulation in ß-cells triggers signals leading to insulin secretion, including changes in ATP/ADP ratio and intracellular calcium levels. Additionally, lipid metabolism and reactive oxygen species (ROS) signaling are essential for ß-cell function and health.

METHODS:

We employed IodoTMT isobaric labeling combined with tandem mass spectrometry to elucidate redox signaling pathways in pancreatic ß-cells.

RESULTS:

Glucose stimulation significantly increases ROS levels in ß-cells, leading to targeted reversible oxidation of proteins involved in key metabolic pathways such as glycolysis, the tricarboxylic acid (TCA) cycle, pyruvate metabolism, oxidative phosphorylation, protein processing in the endoplasmic reticulum (ER), and insulin secretion. Furthermore, the glucose-induced increase in reversible cysteine oxidation correlates with the presence of other post-translational modifications, including acetylation and phosphorylation.

CONCLUSIONS:

Proper functioning of pancreatic ß-cell metabolism relies on fine-tuned regulation, achieved through a sophisticated system of diverse post-translational modifications that modulate protein functions. Our findings demonstrate that glucose induces the production of ROS in pancreatic ß-cells, leading to targeted reversible oxidative modifications of proteins. Furthermore, protein activity is modulated by acetylation and phosphorylation, highlighting the complexity of the regulatory mechanisms in ß-cell function.
Palabras clave

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Metabolism Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Metabolism Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos