ArticleScientific reports2018
CD44 variant inhibits insulin secretion in pancreatic β cells by attenuating LAT1-mediated amino acid uptake.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Overcoming Radiation Resistance: Ferroptosis Induction to Sensitize Solid Tumors to Radiation Therapy.Cancer medicine · 2026Review
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- Insulin resistance and cognitive decline: the metabolic mechanisms linking type 2 diabetes to Alzheimer's disease.Diabetology international · 2025Review
- Changes in pancreatic levodopa uptake in patients with obesity and new-onset type 2 diabetes: an 18F-FDOPA PET-CT study.Frontiers in endocrinology · 2025Article
- Integrated Bioinformatics Analysis Revealed Immune Checkpoint Genes Relevant to Type 2 Diabetes.Diabetes, metabolic syndrome and obesity : targets and therapy · 2024Article
- The human LAT1-4F2hc (SLC7A5-SLC3A2) transporter complex: Physiological and pathophysiological implications.Basic & clinical pharmacology & toxicology · 2023Review
- Inhibition of hyaluronan synthesis prevents β-cell loss in obesity-associated type 2 diabetes.Matrix biology : journal of the International Society for Matrix Biology · 2023Article
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- L-type Amino Acid Transporter 1 Utilizing Ferulic Acid Derivatives Show Increased Drug Delivery in the Mouse Pancreas Along with Decreased Lipid Peroxidation and Prostaglandin Production.Molecular pharmaceutics · 2022Article
- Evaluation of 3-Borono-l-Phenylalanine as a Water-Soluble Boron Neutron Capture Therapy Agent.Pharmaceutics · 2022Article
- Increased CD34 in pancreatic islet negatively predict islet β-cell decrease in type1 diabetes model.Frontiers in physiology · 2022Article
- A graph centrality-based approach for candidate gene prediction for type 1 diabetes.Immunologic research · 2021Article
- Ferroptosis and Its Potential Role in Metabolic Diseases: A Curse or Revitalization?Frontiers in cell and developmental biology · 2021Review
- Article
- Pancreatic Tissue Proteomics Unveils Key Proteins, Pathways, and Networks Associated with Type 1 Diabetes.Proteomics. Clinical applications · 2020Article
- mTOR-Mediated Antioxidant Activation in Solid Tumor Radioresistance.Journal of oncology · 2019Review
- The Human SLC7A5 (LAT1): The Intriguing Histidine/Large Neutral Amino Acid Transporter and Its Relevance to Human Health.Frontiers in chemistry · 2018Review
Corrections and comments
- Erratum issued
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CD44 variant (CD44v) contributes to cancer stemness by stabilizing the xCT subunit of system xc(-) and thereby promoting its glutamate-cystine antiporter activity. CD44 has also been implicated in autoimmune insulitis and inflammation in diabetic islets, but whether CD44v regulates insulin secretion has remained unclear. Here we show that CD44v inhibits insulin secretion by attenuating amino acid transport mediated by the L-type amino acid transporter LAT1. CD44v expression level was inversely related to insulin content in islets of normal and diabetic model mice. Knockdown of CD44 increased insulin secretion, the intracellular insulin level, and the transport of neutral amino acids mediated by LAT1 in Min6 cells. Attenuation of the uptake of neutral amino acids with a LAT inhibitor reduced insulin secretion and insulin content in Min6 cells, whereas overexpression of LAT1 increased insulin secretion. Moreover, inhibition of LAT1 prevented the increase in insulin secretion and content induced by CD44 depletion in Min6 cells. Our results thus implicate CD44v in the regulation of insulin secretion and reveal that amino acid transport is rate limiting for such secretion. They further suggest that amino acid transport mediated by LAT1 is a potential therapeutic target for diabetes.
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