ArticleMolecular and cellular biology2002
Insulin induces heterologous desensitization of G-protein-coupled receptor and insulin-like growth factor I signaling by downregulating beta-arrestin-1.
Article in Molecular and cellular biology, 2002. 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, 75 citations in OpenAlex.
- Targeting receptor tyrosine kinases: from molecular mechanisms to clinical therapeutics.Signal transduction and targeted therapy · 2026Review
- Cellular forgetting, desensitisation, stress and ageing in signalling networks. When do cells refuse to learn more?Cellular and molecular life sciences : CMLS · 2024Review
- The LPAInternational journal of molecular sciences · 2021Review
- Metabolic Functions of G Protein-Coupled Receptors and β-Arrestin-Mediated Signaling Pathways in the Pathophysiology of Type 2 Diabetes and Obesity.Frontiers in endocrinology · 2021Review
- Beta-Arrestins and Receptor Signaling in the Vascular Endothelium.Biomolecules · 2020Review
- Review
- Review
- Insulin-like Growth Factor-I Receptor and Thyroid-Associated Ophthalmopathy.Endocrine reviews · 2019Review
- The Biased G-Protein-Coupled Receptor Agonism Bridges the Gap between the Insulin Receptor and the Metabolic Syndrome.International journal of molecular sciences · 2018Review
- Cross-Talk Between Insulin Signaling and G Protein-Coupled Receptors.Journal of cardiovascular pharmacology · 2017Review
- Heterologous desensitization of cardiac β-adrenergic signal via hormone-induced βAR/arrestin/PDE4 complexes.Cardiovascular research · 2017Article
- Cell-surface receptors transactivation mediated by g protein-coupled receptors.International journal of molecular sciences · 2014Review
- Bioluminescence resonance energy transfer methods to study G protein-coupled receptor-receptor tyrosine kinase heteroreceptor complexes.Methods in cell biology · 2013Article
- G protein-coupled receptor kinase 2 plays a relevant role in insulin resistance and obesity.Diabetes · 2010Article
- Arrestin development: emerging roles for beta-arrestins in developmental signaling pathways.Developmental cell · 2009Review
- Homocysteine effects classical pathway of GPCR down regulation: Galpha(q/11), Galpha(12/13), G(i/o).Molecular and cellular biochemistry · 2009Article
- IGF-1 regulates cAMP levels in astrocytes through a beta2-adrenergic receptor-dependant mechanism.International journal of medical sciences · 2008Article
- Beta-Arrestin-1 mediates glucagon-like peptide-1 signaling to insulin secretion in cultured pancreatic beta cells.Proceedings of the National Academy of Sciences of the United States of America · 2008Article
- Heterotrimeric G proteins and the single-transmembrane domain IGF-II/M6P receptor: functional interaction and relevance to cell signaling.Molecular neurobiology · 2007Review
- beta-arrestin-1 competitively inhibits insulin-induced ubiquitination and degradation of insulin receptor substrate 1.Molecular and cellular biology · 2004Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
beta-Arrestin-1 mediates agonist-dependent desensitization and internalization of G protein-coupled receptors (GPCRs) and is also essential for GPCR mitogenic signaling. In addition, insulin-like growth factor I receptor (IGF-IR) endocytosis is facilitated by beta-arrestin-1, and internalization is necessary for IGF-I-stimulated mitogen-activated protein (MAP) kinase activation. Here, we report that treatment of cells for 12 h with insulin (100 ng/ml) induces an approximately 50% decrease in cellular beta-arrestin-1 content due to ubiquitination of beta-arrestin-1 and proteosome-mediated degradation. This insulin-induced decrease in beta-arrestin-1 content was blocked by inhibition of phosphatidylinositol-3 kinase (PI-3 kinase) and MEK with wortmannin and PD98059, respectively. We also found a marked decrease in the association of beta-arrestin-1 with the IGF-IR and a 55% inhibition of IGF-I-stimulated MAP kinase phosphorylation. In insulin-treated, beta-arrestin-1-downregulated cells, there was complete inhibition of lysophosphatidic acid (LPA) or isoproterenol (ISO)-stimulated MAP kinase phosphorylation. This was associated with a decrease in beta-arrestin-1 association with the beta2-AR as well as a decrease in beta-arrestin-1-Src and Src-beta2-AR association. Ectopic expression of wild-type beta-arrestin-1 in insulin-treated cells in which endogenous beta-arrestin-1 had been downregulated rescued IGF-I- and LPA-stimulated MAP kinase phosphorylation. In conclusion, we found the following. (i) Chronic insulin treatment leads to enhanced beta-arrestin-1 degradation. (ii) This downregulation of endogenous beta-arrestin-1 is associated with decreased IGF-I-, LPA-, and ISO-mediated MAP kinase signaling, which can be rescued by ectopic expression of wild-type beta-arrestin-1. (iii) Finally, these results describe a novel mechanism for heterologous desensitization, whereby insulin treatment can impair GPCR signaling, and highlight the importance of beta-arrestin-1 as a target molecule for this desensitization mechanism.
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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.