ArticleThe Journal of biological chemistry2010
GLP-1 mediates antiapoptotic effect by phosphorylating Bad through a beta-arrestin 1-mediated ERK1/2 activation in pancreatic beta-cells.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers.
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Who cites it
111 citing papers in PubMed, 181 citations in OpenAlex.
- Loss of Intestinal MSTN Promotes GLP-1 Secretion Through SGLT1 Palmitoylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Adipose Tissue Remodeling Beyond Weight Loss: New Insights Into Incretin-Based Therapies and Bariatric Surgery.Current obesity reports · 2026Review
- Gestational diabetes: from pathogenesis to therapeutic intervention.Diabetology & metabolic syndrome · 2026Review
- Modelling G protein-biased agonism using GLP-1 receptor C-terminal mutations.Molecular metabolism · 2026Article
- Glucagon-like Peptide-1 Receptor Dependent Signaling in Cardiovascular Health and Disease: A Mini-review.Journal of cardiovascular translational research · 2026Review
- Spatially diffuse cAMP signalling with oppositely biased GLP-1 receptor agonists in β-cells despite differences in receptor localisation.Molecular metabolism · 2026Article
- Curcumin Promotes Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells from Anterior Cruciate Ligament Reconstruction via ERK1/2 Pathway.Current medicinal chemistry · 2026Article
- Review
- Incretins and SGLT-2 inhibitors in diabetic patients with neuroendocrine tumors: current updates and future directions.Reviews in endocrine & metabolic disorders · 2025Review
- Article
- Biased agonism of GLP-1R and GIPR enhances glucose lowering and weight loss, with dual GLP-1R/GIPR biased agonism yielding greater efficacy.Cell reports. Medicine · 2025Article
- Unlocking the multifaceted roles of GLP-1: Physiological functions and therapeutic potential.Toxicology reports · 2025Review
- Antidiabetic GLP-1 Receptor Agonists Have Neuroprotective Properties in Experimental Animal Models of Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Arrestin-independent internalization of the GLP-1 receptor is facilitated by a GRK, clathrin, and caveolae-dependent mechanism.The FEBS journal · 2025Article
- G-Protein-Coupled Receptor (GPCR) Signaling and Pharmacology in Metabolism: Physiology, Mechanisms, and Therapeutic Potential.Biomolecules · 2025Review
- Dysfunctional β-cell autophagy induces β-cell stress and enhances islet immunogenicity.Frontiers in immunology · 2025Article
- Variable GLP-1 receptor expression across diverse neuroendocrine neoplasms: implications for incretin therapies.Endocrine oncology (Bristol, England) · 2025Article
- Mechanistic Pathways and Clinical Implications of GLP-1 Receptor Agonists in Type 1 Diabetes Management.International journal of molecular sciences · 2024Review
- Adipose Tissue: A Novel Target of the Incretin Axis? A Paradigm Shift in Obesity-Linked Insulin Resistance.International journal of molecular sciences · 2024Review
- Review
51 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Strategies based on activating GLP-1 receptor (GLP-1R) are intensively developed for the treatment of type 2 diabetes. The exhaustive knowledge of the signaling pathways linked to activated GLP-1R within the beta-cells is of major importance. In beta-cells, GLP-1 activates the ERK1/2 cascade by diverse pathways dependent on either Galpha(s)/cAMP/cAMP-dependent protein kinase (PKA) or beta-arrestin 1, a scaffold protein. Using pharmacological inhibitors, beta-arrestin 1 small interfering RNA, and islets isolated from beta-arrestin 1 knock-out mice, we demonstrate that GLP-1 stimulates ERK1/2 by two temporally distinct pathways. The PKA-dependent pathway mediates rapid and transient ERK1/2 phosphorylation that leads to nuclear translocation of the activated kinases. In contrast, the beta-arrestin 1-dependent pathway produces a late ERK1/2 activity that is restricted to the beta-cell cytoplasm. We further observe that GLP-1 phosphorylates the cytoplasmic proapoptotic protein Bad at Ser-112 but not at Ser-155. We find that the beta-arrestin 1-dependent ERK1/2 activation engaged by GLP-1 mediates the Ser-112 phosphorylation of Bad, through p90RSK activation, allowing the association of Bad with the scaffold protein 14-3-3, leading to its inactivation. beta-Arrestin 1 is further found to mediate the antiapoptotic effect of GLP-1 in beta-cells through the ERK1/2-p90RSK-phosphorylation of Bad. This new regulatory mechanism engaged by activated GLP-1R involving a beta-arrestin 1-dependent spatiotemporal regulation of the ERK1/2-p90RSK activity is now suspected to participate in the protection of beta-cells against apoptosis. Such signaling mechanism may serve as a prototype to generate new therapeutic GLP-1R ligands.
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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.