ArticleMolecular metabolism2018
Neuraminidase 1 activates insulin receptor and reverses insulin resistance in obese mice.
Article in Molecular metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Mammalian Neuraminidases in Immune-Mediated Diseases: Mucins and Beyond.Frontiers in immunology · 2022Pooled it
- A non-enzymatic function of neuraminidase 1 restrains hepatic glucagon response in mice.Nature communications · 2026Article
- Loss of neuraminidase 1 inhibits the activation of hepatic stellate cells through TGF-β/Smad3 signaling.Iranian journal of basic medical sciences · 2026Article
- The Emerging Role of Sialic Acids in Obesity and Diabetes: Molecular Mechanisms and Therapeutic Perspectives.Biomolecules · 2025Review
- Sialidases as Potential Therapeutic Targets for Treatment of a Number of Human Diseases.International journal of molecular sciences · 2025Review
- Neuraminidase 1 Exacerbated Glycolytic Dysregulation and Cardiotoxicity by Destabilizing SIRT1 through Interactions with NRF2 and HIF1α.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- NEU1-Mediated Extracellular Vesicle Glycosylation in Alzheimer's Disease: Mechanistic Insights into Intercellular Communication and Therapeutic Targeting.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Article
- Neuraminidase-1 (NEU1): Biological Roles and Therapeutic Relevance in Human Disease.Current issues in molecular biology · 2024Review
- Sialic acids cleavage induced by elastin-derived peptides impairs the interaction between insulin and its receptor in adipocytes 3T3-L1.Journal of physiology and biochemistry · 2024Article
- Plasma Metabolites and Life's Simple 7 in REGARDS.Stroke · 2024Article
- Article
- Severe kidney dysfunction in sialidosis mice reveals an essential role for neuraminidase 1 in reabsorption.JCI insight · 2023Article
- Human Milk Oligosaccharides in Maternal Serum Respond to Oral Glucose Load and Are Associated with Insulin Sensitivity.Nutrients · 2023Article
- Correlation of Serum N-Acetylneuraminic Acid with the Risk of Moyamoya Disease.Brain sciences · 2023Article
- Structure of the immunoregulatory sialidase NEU1.Science advances · 2023Article
- Bioinformatics Analysis of Next Generation Sequencing Data Identifies Molecular Biomarkers Associated With Type 2 Diabetes Mellitus.Clinical medicine insights. Endocrinology and diabetes · 2023Article
- Sialidase Inhibitors with Different Mechanisms.Journal of medicinal chemistry · 2022Review
- Neuraminidase-1: A Sialidase Involved in the Development of Cancers and Metabolic Diseases.Cancers · 2022Review
- Glucosamine amends CNS pathology in mucopolysaccharidosis IIIC mouse expressing misfolded HGSNAT.The Journal of experimental medicine · 2022Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
Abstract
objectivesNeuraminidase 1 (NEU1) cleaves terminal sialic acids of glycoconjugates during lysosomal catabolism. It also modulates the structure and activity of cellular surface receptors affecting diverse pathways. Previously we demonstrated that NEU1 activates the insulin receptor (IR) and that NEU1-deficient CathA
methodsTo test if desialylation causes a conformational change in the IR dimer we measured interaction between the receptor subunits by Bioluminescence Resonance Energy Transfer in the HEK293T cells either overexpressing NEU1 or treated with the NEU1 inhibitor. The influence of NEU1 overexpression on insulin resistance was studied in vitro in palmitate-treated HepG2 cells transduced with NEU1-expressing lentivirus and in vivo in C57Bl6 mice treated with HFD and either pharmacological inducer of NEU1, Ambroxol or NEU1-expressing adenovirus. NEU1-deficient CathA
resultsBy desialylation of IR, NEU1 induced formation of its active dimer leading to insulin signaling. Overexpression of NEU1 in palmitate-treated HepG2 cells restored insulin signaling, suggesting that increased NEU1 levels may reverse insulin resistance. Five-day treatment of glycemic C57Bl6 mice receiving HFD with the activator of the lysosomal gene network, Ambroxol, increased NEU1 expression and activity in muscle tissue, normalized fasting glucose levels, and improved physiological and molecular responses to glucose and insulin. Ambroxol did not improve insulin sensitivity in obese insulin-resistant CathA
conclusionTogether our results demonstrate that increase of NEU1 activity in insulin target tissues reverses insulin resistance and glucose intolerance suggesting that a pharmacological modulation of NEU1 activity may be potentially explored for restoring insulin sensitivity and resolving hyperglycemia associated with T2DM.
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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.