ArticleMolecular metabolism2014
CREB mediates the insulinotropic and anti-apoptotic effects of GLP-1 signaling in adult mouse β-cells.
Article in Molecular metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 2 of them syntheses that pooled it.
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Who cites it
41 citing papers in PubMed, 2 syntheses or guidelines pooled it, 62 citations in OpenAlex.
- Discovery of 318 new risk loci for type 2 diabetes and related vascular outcomes among 1.4 million participants in a multi-ancestry meta-analysis.Nature genetics · 2020Pooled it
- Pooled it
- c-Jun N-terminal kinase 3 as a permissive regulator of β-cell incretin responsiveness.Journal of diabetes investigation · 2026Article
- Proteomic analyses of human islets reveal potential markers of β cell dysfunction during prediabetes.JCI insight · 2026Article
- Tomosyn-2 Regulates Postnatal β-Cell Expansion and Insulin Secretion to Maintain Glucose Homeostasis.Diabetes · 2026Article
- Med14 phosphorylation shapes genomic response to GLP-1 agonists.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The Multifaceted Nature of GLP-1: Molecular Mechanisms and Signaling Pathways in Metabolic and Neurodegenerative Diseases.International journal of molecular sciences · 2026Review
- Glucagon-like peptide-1: a new potential regulator for mesenchymal stem cells in the treatment of type 2 diabetes mellitus and its complication.Stem cell research & therapy · 2025Review
- GLP-1 and GIP agonism has no direct actions in human hepatocytes or hepatic stellate cells.Cellular and molecular life sciences : CMLS · 2024Article
- Glucagon-Like Peptide-1: New Regulator in Lipid Metabolism.Diabetes & metabolism journal · 2024Review
- GLP-1 signaling-regulated SNAP25 is involved in improved insulin secretion in diabetic GK rats after Roux-en-Y gastric bypass surgery.Molecular biology reports · 2024Article
- Ubiquitination and Metabolic Disease.Advances in experimental medicine and biology · 2024Review
- Stress-induced β cell early senescence confers protection against type 1 diabetes.Cell metabolism · 2023Article
- Review
- Regulation of insulin secretion by the post-translational modifications.Frontiers in cell and developmental biology · 2023Review
- Reduced miR-184-3p expression protects pancreatic β-cells from lipotoxic and proinflammatory apoptosis in type 2 diabetes via CRTC1 upregulation.Cell death discovery · 2022Article
- A multiancestry genome-wide association study of unexplained chronic ALT elevation as a proxy for nonalcoholic fatty liver disease with histological and radiological validation.Nature genetics · 2022Article
- Gsα-dependent signaling is required for postnatal establishment of a functional β-cell mass.Molecular metabolism · 2021Article
- Mechanisms of Beta-Cell Apoptosis in Type 2 Diabetes-Prone Situations and Potential Protection by GLP-1-Based Therapies.International journal of molecular sciences · 2021Review
- Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice.Nature microbiology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
objectiveGlucagon-like peptide-1 (GLP-1) plays a major role in pancreatic β-cell function and survival by increasing cytoplasmic cAMP levels, which are thought to affect transcription through activation of the basic leucine zipper (bZIP) transcription factor CREB. Here, we test CREB function in the adult β-cell through inducible gene deletion.
methodsWe employed cell type-specific and inducible gene ablation to determine CREB function in pancreatic β-cells in mice.
resultsBy ablating CREB acutely in mature β-cells in tamoxifen-treated Creb (loxP/loxP);Pdx1-CreERT2 mice, we show that CREB has little impact on β-cell turnover, in contrast to what had been postulated previously. Rather, CREB is required for GLP-1 to elicit its full effects on stimulating glucose-induced insulin secretion and protection from cytokine-induced apoptosis. Mechanistically, we find that CREB regulates expression of the pro-apoptotic gene p21 (Cdkn1a) in β-cells, thus demonstrating that CREB is essential to mediating this critical aspect of GLP-1 receptor signaling.
conclusionsIn sum, our studies using conditional gene deletion put into question current notions about the importance of CREB in regulating β-cell function and mass. However, we reveal an important role for CREB in the β-cell response to GLP-1 receptor signaling, further validating CREB as a therapeutic target for diabetes.
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