ArticleDiabetologia2012
Carbohydrate response element-binding protein (ChREBP) plays a pivotal role in beta cell glucotoxicity.
Article in Diabetologia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 82 citations in OpenAlex.
- Temporal single-cell transcriptional dynamics of murine pancreatic islet remodeling during hyperglycaemia progression.Molecular metabolism · 2026Article
- MondoA mediates transcriptional coordination between the MYC network and the integrated stress response in pancreatic cancer.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Unraveling the role of ChREBP in lung adenocarcinoma: Expression, regulatory networks, and potential functional impact.PloS one · 2026Article
- Cross-lag association between TyG-CVAI and frailty index: evidence from a natural population cohort in southwestern China.Frontiers in public health · 2026Article
- Deficiency of SCAMP5 Triggers Pancreatic β-Cell Secretory Dysfunction and Apoptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Triglycerides, Glucose Metabolism, and Type 2 Diabetes.International journal of molecular sciences · 2025Review
- MondoA mediates transcriptional coordination between the MYC network and the integrated stress response in pancreatic ductal adenocarcinoma.bioRxiv : the preprint server for biology · 2025Article
- Glycosylation in kidney diseases.Precision clinical medicine · 2025Review
- Carbohydrate response element-binding protein (ChREBP) mediates decreased SNAP25 expression in islets from diabetic Goto-Kakizaki (GK) rats.FEBS open bio · 2024Article
- A critical review on diabetes mellitus type 1 and type 2 management approaches: from lifestyle modification to current and novel targets and therapeutic agents.Frontiers in endocrinology · 2024Review
- A Supportive Role of Mesenchymal Stem Cells on Insulin-Producing Langerhans Islets with a Specific Emphasis on The Secretome.Biomedicines · 2023Review
- The role of ChREBP in carbohydrate sensing and NAFLD development.Nature reviews. Endocrinology · 2023Review
- The Function of MondoA and ChREBP Nutrient-Sensing Factors in Metabolic Disease.International journal of molecular sciences · 2023Review
- Ablation of GPR56 Causes β-Cell Dysfunction by ATP Loss through Mistargeting of Mitochondrial VDAC1 to the Plasma Membrane.Biomolecules · 2023Article
- Cadmium Toxicity Is Regulated by Peroxisome Proliferator-Activated Receptor δ in Human Proximal Tubular Cells.International journal of molecular sciences · 2022Article
- Maladaptive positive feedback production of ChREBPβ underlies glucotoxic β-cell failure.Nature communications · 2022Article
- Thioredoxin-interacting protein in diabetic retinal neurodegeneration: A novel potential therapeutic target for diabetic retinopathy.Frontiers in neuroscience · 2022Review
- Insulin-Responsive Transcription Factors.Biomolecules · 2021Review
- The Roles of Carbohydrate Response Element Binding Protein in the Relationship between Carbohydrate Intake and Diseases.International journal of molecular sciences · 2021Review
- From Food to Genes: Transcriptional Regulation of Metabolism by Lipids and Carbohydrates.Nutrients · 2021Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
aims/hypothesisThis study was aimed at the elucidation of the pathogenesis of glucotoxicity, i.e. the mechanism whereby hyperglycaemia damages pancreatic beta cells. The identification of pathways in the process may help identify targets for beta cell-protective therapy. Carbohydrate response element-binding protein (ChREBP), a transcription factor that regulates the expression of multiple hyperglycaemia-induced genes, is produced in abundance in pancreatic beta cells. We hypothesise that ChREBP plays a pivotal role in mediating beta cell glucotoxicity.
methodsWe assessed the role of ChREBP in glucotoxicity in 832/13 beta cells, isolated mouse islets and human pancreas tissue sections using multiple complementary approaches under control and high-glucose-challenge conditions as well as in adeno-associated virus-induced beta cell-specific overexpression of Chrebp (also known as Mlxipl) in mice.
resultsUnder both in vitro and in vivo conditions, ChREBP activates downstream target genes, including fatty acid synthase and thioredoxin-interacting protein, leading to lipid accumulation, increased oxidative stress, reduced insulin gene transcription/secretion and enhanced caspase activity and apoptosis, processes that collectively define glucotoxicity. Immunoreactive ChREBP is enriched in the nucleuses of beta cells in pancreatic tissue sections from diabetic individuals compared with non-diabetic individuals. Finally, we demonstrate that induced beta cell-specific Chrebp overexpression is sufficient to phenocopy the glucotoxicity manifestations of hyperglycaemia in mice in vivo. CONCLUSIONS/
interpretationThese data indicate that ChREBP is a key transcription factor that mediates many of the hyperglycaemia-induced activations in a gene expression programme that underlies beta cell glucotoxicity at the molecular, cellular and whole animal levels.
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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.