ArticleCell reports2014
APPL1 potentiates insulin sensitivity by facilitating the binding of IRS1/2 to the insulin receptor.
Article in Cell reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
What it found
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Who cites it
71 citing papers in PubMed, 130 citations in OpenAlex.
- Gut Microbiota, Diet and Lipid Metabolism in Adolescents with NAFLD and Their Role in Preventive Strategies.International journal of molecular sciences · 2026Review
- Insulin receptor trafficking and interactions in muscle cells.Journal of the Endocrine Society · 2026Article
- Dysregulated miRNAs Targeting Adiponectin Signaling in Colorectal Cancer.International journal of molecular sciences · 2025Review
- Obesity-cancer axis crosstalk: Molecular insights and therapeutic approaches.Acta pharmaceutica Sinica. B · 2025Review
- Adiponectin and Adiponectin Receptors in Atherosclerosis.Endocrine reviews · 2025Review
- Assessment of pathogenicity and functional characterization ofWorld journal of diabetes · 2024Article
- Adiponectin Resistance in Obesity: Adiponectin Leptin/Insulin Interaction.Advances in experimental medicine and biology · 2024Review
- The Role of Adipokines in the Pathogenesis of Psoriasis.International journal of molecular sciences · 2023Review
- Integrated transcriptome analysis identifies APPL1/RPS6KB2/GALK1 as immune-related metastasis factors in breast cancer.Open medicine (Warsaw, Poland) · 2023Article
- Glucagon-like peptide-1 (GLP-1) receptor agonists and neuroinflammation: Implications for neurodegenerative disease treatment.Pharmacological research · 2022Review
- Severe choline deficiency induces alternative splicing aberrance in optimized duck primary hepatocyte cultures.Animal bioscience · 2022Article
- Adiponectin: friend or foe in obesity and inflammation.Medical review (2021) · 2022Review
- Regulation of Metabolic Health by an "Olfactory-Hypothalamic Axis" and Its Possible Implications for the Development of Therapeutic Approaches for Obesity and T2D.Cellular and molecular neurobiology · 2022Review
- Participation of OCRL1, and APPL1, in the expression, proteolysis, phosphorylation and endosomal trafficking of megalin: Implications for Lowe Syndrome.Frontiers in cell and developmental biology · 2022Article
- Central Adiponectin Signaling - A Metabolic Regulator in Support of Brain Plasticity.Brain plasticity (Amsterdam, Netherlands) · 2022Review
- Adipokines, Hepatokines and Myokines: Focus on Their Role and Molecular Mechanisms in Adipose Tissue Inflammation.Frontiers in endocrinology · 2022Review
- Article
- AMPK-mediated phosphorylation enhances the auto-inhibition of TBC1D17 to promote Rab5-dependent glucose uptake.Cell death and differentiation · 2021Article
- Adiponectin: a potential target for obesity-associated Alzheimer's disease.Metabolic brain disease · 2021Review
- Adaptor protein APPL1 links neuronal activity to chromatin remodeling in cultured hippocampal neurons.Journal of molecular cell biology · 2021Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 1 country.
Funding
Abstract
Binding of insulin receptor substrate proteins 1 and 2 (IRS1/2) to the insulin receptor (IR) is essential for the regulation of insulin sensitivity and energy homeostasis. However, the mechanism of IRS1/2 recruitment to the IR remains elusive. Here, we identify adaptor protein APPL1 as a critical molecule that promotes IRS1/2-IR interaction. APPL1 forms a complex with IRS1/2 under basal conditions, and this complex is then recruited to the IR in response to insulin or adiponectin stimulation. The interaction between APPL1 and IR depends on insulin- or adiponectin-stimulated APPL1 phosphorylation, which is greatly reduced in insulin target tissues in obese mice. appl1 deletion in mice consistently leads to systemic insulin resistance and a significant reduction in insulin-stimulated IRS1/2, but not IR, tyrosine phosphorylation, indicating that APPL1 sensitizes insulin signaling by acting at a site downstream of the IR. Our study uncovers a mechanism regulating insulin signaling and crosstalk between the insulin and adiponectin pathways.
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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.