ArticleMolecular metabolism2016
Islet ChREBP-β is increased in diabetes and controls ChREBP-α and glucose-induced gene expression via a negative feedback loop.
Article in Molecular metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 40 citations in OpenAlex.
- ChREBP-β Exacerbates Renal Tubular Disorders Caused by Fructose via ATF4.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Role of ChREBP-PPARα-FGF21 Axis in Metabolic Dysfunction of MASLD.International journal of molecular sciences · 2025Article
- Anti-inflammatory mechanism of total flavonoids fromFrontiers in immunology · 2025Article
- Mbnl1-mediated alternative splicing of circMlxipl regulates Rbbp6-involved ChREBP turnover to inhibit lipotoxicity-induced β-cell damage.Molecular medicine (Cambridge, Mass.) · 2024Article
- Calorie restriction increases insulin sensitivity to promote beta cell homeostasis and longevity in mice.Nature communications · 2024Article
- The Function of MondoA and ChREBP Nutrient-Sensing Factors in Metabolic Disease.International journal of molecular sciences · 2023Review
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- Review
- Network-based identification and prioritization of key transcriptional factors of diabetic kidney disease.Computational and structural biotechnology journal · 2023Article
- Maladaptive positive feedback production of ChREBPβ underlies glucotoxic β-cell failure.Nature communications · 2022Article
- Article
- The Roles of Carbohydrate Response Element Binding Protein in the Relationship between Carbohydrate Intake and Diseases.International journal of molecular sciences · 2021Review
- Activation of the mitogen-activated protein kinase ERK1/2 signaling pathway suppresses the expression of ChREBPα and β in HepG2 cells.FEBS open bio · 2021Article
- From Food to Genes: Transcriptional Regulation of Metabolism by Lipids and Carbohydrates.Nutrients · 2021Review
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- The Protective Role of the Carbohydrate Response Element Binding Protein in the Liver: The Metabolite Perspective.Frontiers in endocrinology · 2020Review
- Glucose-Sensing Transcription Factor MondoA/ChREBP as Targets for Type 2 Diabetes: Opportunities and Challenges.International journal of molecular sciences · 2019Review
- FMK, an Inhibitor of p90RSK, Inhibits High Glucose-Induced TXNIP Expression via Regulation of ChREBP in Pancreatic β Cells.International journal of molecular sciences · 2019Article
- Nutritional Regulation of Gene Expression: Carbohydrate-, Fat- and Amino Acid-Dependent Modulation of Transcriptional Activity.International journal of molecular sciences · 2019Review
- Activation of Nrf2 Is Required for Normal and ChREBPα-Augmented Glucose-Stimulated β-Cell Proliferation.Diabetes · 2018Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
objectiveCarbohydrate-response element-binding protein (ChREBP) is the major transcription factor conferring glucose-induced gene expression in pancreatic islets, liver and adipose tissue. Recently, a novel ChREBP isoform, ChREBP-β, was identified in adipose tissue and found to be also expressed in islets and involved in glucose-induced beta cell proliferation. However, the physiological function of this less abundant β-isoform in the islet, and in diabetes, is largely unknown. The aims of the present study, therefore, were to determine how diabetes affects ChREBP-β and elucidate its physiological role in pancreatic beta cells.
methodsNon-obese diabetic and obese, diabetic ob/ob mice were used as models of T1D and T2D and human islets and the rat INS-1 beta cell line were exposed to low/high glucose and used for ChREBP isoform-specific gain-and-loss-of-function experiments. Changes in ChREBP-β and ChREBP-α were assessed by qRT-PCR, immunoblotting, promoter luciferase, and chromatin immunoprecipitation studies.
resultsExpression of the ChREBP-β isoform was highly induced in diabetes and by glucose, whereas ChREBP-α was downregulated. Interestingly, ChREBP-β gain-of-function experiments further revealed that it was ChREBP-β that downregulated ChREBP-α through a negative feedback loop. On the other hand, ChREBP-β knockdown led to unabated ChREBP-α activity and glucose-induced expression of target genes, suggesting that one of the physiological roles of this novel β-isoform is to help keep glucose-induced and ChREBP-α-mediated gene expression under control.
conclusionsWe have identified a previously unappreciated negative feedback loop by which glucose-induced ChREBP-β downregulates ChREBP-α-signaling providing new insight into the physiological role of islet ChREBP-β and into the regulation of glucose-induced gene expression.
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