ArticleEndocrinology2014
High glucose exposure promotes activation of protein phosphatase 2A in rodent islets and INS-1 832/13 β-cells by increasing the posttranslational carboxylmethylation of its catalytic subunit.
Article in Endocrinology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- Pathophysiological Mechanisms of Diabetes-Induced Macrovascular and Microvascular Complications: The Role of Oxidative Stress.Medical sciences (Basel, Switzerland) · 2025Review
- Unraveling the Mystery of Insulin Resistance: From Principle Mechanistic Insights and Consequences to Therapeutic Interventions.International journal of molecular sciences · 2025Review
- Saturated fatty acids stimulate cytokine production in tanycytes via the PP2Ac-dependent signaling pathway.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- The dance of proteostasis and metabolism: Unveiling the caloristatic controlling switch.Cell stress & chaperones · 2024Review
- Heat shock response during the resolution of inflammation and its progressive suppression in chronic-degenerative inflammatory diseases.Cell stress & chaperones · 2024Review
- PP2Ac knockdown attenuates lipotoxicity‑induced pancreatic β‑cell dysfunction and apoptosis.Experimental and therapeutic medicine · 2023Article
- Protein Phosphatase 2A: Role in T Cells and Diseases.Journal of immunology research · 2023Review
- Biased holoenzyme assembly of protein phosphatase 2A (PP2A): From cancer to small molecules.The Journal of biological chemistry · 2022Review
- Alpha4 contributes to the dysfunction of the pancreatic beta cell under metabolic stress.Molecular and cellular endocrinology · 2022Article
- Ser/Thr phosphatases: One of the key regulators of insulin signaling.Reviews in endocrine & metabolic disorders · 2022Review
- Protein Phosphatase 2A Deficiency in Macrophages Increases Foam Cell Formation and Accelerates Atherosclerotic Lesion Development.Frontiers in cardiovascular medicine · 2021Article
- Potential roles of PP2A-Rac1 signaling axis in pancreatic β-cell dysfunction under metabolic stress: Progress and promise.Biochemical pharmacology · 2020Review
- Proteomics and phosphoproteomics study of LCMT1 overexpression and oxidative stress: overexpression of LCMT1 arrests HRedox report : communications in free radical research · 2019Article
- Targeting PP2A in cancer: Combination therapies.Biochimica et biophysica acta. Molecular cell research · 2019Review
- A high glucose diet induces autophagy in a HLH-30/TFEB-dependent manner and impairs the normal lifespan ofAging · 2018Article
- RACking up ceramide-induced islet β-cell dysfunction.Biochemical pharmacology · 2018Review
- Knockdown of GSK3β increases basal autophagy and AMPK signalling in nutrient-laden human aortic endothelial cells.Bioscience reports · 2016Article
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- Quantitative proteomics reveals novel protein interaction partners of PP2A catalytic subunit in pancreatic β-cells.Molecular and cellular endocrinology · 2016Article
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 1 country.
Funding
Abstract
Existing evidence implicates regulatory roles for protein phosphatase 2A (PP2A) in a variety of cellular functions, including cytoskeletal remodeling, hormone secretion, and apoptosis. We report here activation of PP2A in normal rat islets and insulin-secreting INS-1 832/13 cells under the duress of hyperglycemic (HG) conditions. Small interfering RNA-mediated knockdown of the catalytic subunit of PP2A (PP2Ac) markedly attenuated glucose-induced activation of PP2A. HG, but not nonmetabolizable 3-O-methyl glucose or mannitol (osmotic control), significantly stimulated the methylation of PP2Ac at its C-terminal Leu-309, suggesting a novel role for this posttranslational modification in glucose-induced activation of PP2A. Moreover, knockdown of the cytosolic leucine carboxymethyl transferase 1 (LCMT1), which carboxymethylates PP2Ac, significantly attenuated PP2A activation under HG conditions. In addition, HG conditions, but not 3-O-methyl glucose or mannitol, markedly increased the expression of LCMT1. Furthermore, HG conditions significantly increased the expression of B55α, a regulatory subunit of PP2A, which has been implicated in islet dysfunction under conditions of oxidative stress and diabetes. Thapsigargin, a known inducer of endoplasmic reticulum stress, failed to exert any discernible effects on the carboxymethylation of PP2Ac, expression of LCMT1 and B55α, or PP2A activity, suggesting no clear role for endoplasmic reticulum stress in HG-induced activation of PP2A. Based on these findings, we conclude that exposure of the islet β-cell to HG leads to accelerated PP2A signaling pathway, leading to loss in glucose-induced insulin secretion.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.