ArticleCell communication and signaling : CCS2019
Glucose-dependent phosphorylation signaling pathways and crosstalk to mitochondrial respiration in insulin secreting cells.
Article in Cell communication and signaling : CCS, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Biological and Nutritional Applications of Microalgae.Nutrients · 2024Review
- Multi-omic human pancreatic islet endoplasmic reticulum and cytokine stress response mapping provides type 2 diabetes genetic insights.Cell metabolism · 2024Article
- Interplay of Glucose Metabolism and Hippo Pathway in Chondrocytes: Pathophysiology and Therapeutic Targets.Bioengineering (Basel, Switzerland) · 2024Review
- Glucosamine substituted sulfonylureas: IRS-PI3K-PKC-AKT-GLUT4 insulin signalling pathway intriguing agent.RSC medicinal chemistry · 2024Article
- Alpha4 contributes to the dysfunction of the pancreatic beta cell under metabolic stress.Molecular and cellular endocrinology · 2022Article
- Black Truffle Extract Exerts Antidiabetic Effects through Inhibition of Inflammation and Lipid Metabolism Regulation.Oxidative medicine and cellular longevity · 2022Article
- Review
- Mitochondrial hydrogen peroxide positively regulates neuropeptide secretion during diet-induced activation of the oxidative stress response.Nature communications · 2021Article
- Integration of single-cell datasets reveals novel transcriptomic signatures of β-cells in human type 2 diabetes.NAR genomics and bioinformatics · 2020Article
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Authors and funding
7 authors.
Funding
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Abstract
backgroundGlucose is the main secretagogue of pancreatic beta-cells. Uptake and metabolism of the nutrient stimulates the beta-cell to release the blood glucose lowering hormone insulin. This metabolic activation is associated with a pronounced increase in mitochondrial respiration. Glucose stimulation also initiates a number of signal transduction pathways for the coordinated regulation of multiple biological processes required for insulin secretion.
methodsShotgun proteomics including TiO
resultsOur kinetic analysis of substrate phosphorylation reveal the molecular mechanism leading to rapid activation of insulin biogenesis, vesicle trafficking, insulin granule exocytosis and cytoskeleton remodeling. Kinase-substrate enrichment identified upstream kinases and phosphatases and time-dependent activity changes during glucose stimulation. Activity trajectories of well-known glucose-regulated kinases and phosphatases are described. In addition, we predict activity changes in a number of kinases including NUAK1, not or only poorly studied in the context of the pancreatic beta-cell. Furthermore, we pharmacologically tested whether signaling pathways predicted by kinase-substrate enrichment analysis affected glucose-dependent acceleration of mitochondrial respiration. We find that phosphoinositide 3-kinase, Ca2+/calmodulin dependent protein kinase and protein kinase C contribute to short-term regulation of energy metabolism.
conclusionsOur results provide a global view into the regulation of kinases and phosphatases in insulin secreting cells and suggest cross talk between glucose-induced signal transduction and mitochondrial activation.
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