ArticleInternational journal of biological sciences2017
Intracellular Insulin and Impaired Autophagy in a Zebrafish model and a Cell Model of Type 2 diabetes.
Article in International journal of biological sciences, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 43 citations in OpenAlex.
- Autophagy and metabolic homeostasis: Exploration in obesity‑related metabolic diseases (Review).International journal of molecular medicine · 2026Review
- Structural and Physicochemical Properties ofNutrients · 2025Article
- Zebrafish as an effective model for accelerating diabetes research from discovery to therapy.Journal of diabetes and metabolic disorders · 2025Review
- Preclinical research in obesity-associated metabolic diseases using in vitro, multicellular, and non-mammalian models.Journal of physiology and biochemistry · 2025Review
- Zebrafish as a preclinical model for diabetes mellitus and its complications: From monogenic to gestational diabetes and beyond.World journal of diabetes · 2025Review
- mInternational journal of molecular sciences · 2025Article
- Type 2 Diabetes Induces Mitochondrial Dysfunction in Zebrafish Skeletal Muscle Leading to Diabetic Myopathy via the miR-139-5p/NAMPT Pathway.International journal of molecular sciences · 2025Article
- Autophagy-lysosome pathway in insulin & glucagon homeostasis.Frontiers in endocrinology · 2025Review
- mTOR Dysregulation, Insulin Resistance, and Hypertension.Biomedicines · 2024Review
- Beyond drug discovery: Exploring the physiological and methodological dimensions of zebrafish in diabetes research.Experimental physiology · 2024Review
- Imaging analytical technique to assess gastrointestinal motility in vivo using zebrafish larvae with diabetes mellitus-like traits.PloS one · 2024Article
- Non-Genetic-Induced Zebrafish Model for Type 2 Diabetes with Emphasis on Tools in Model Validation.International journal of molecular sciences · 2023Review
- An Association between Insulin Resistance and Neurodegeneration in Zebrafish Larval Model (International journal of molecular sciences · 2022Article
- Autophagy inhibits cancer stemness in triple-negative breast cancer via miR-181a-mediated regulation of ATG5 and/or ATG2B.Molecular oncology · 2022Article
- Article
- The effects of autophagy in rat tracheal epithelial cells induced by silver nanoparticles.Environmental science and pollution research international · 2021Article
- A novel palmitic acid hydroxy stearic acid (5-PAHSA) plays a neuroprotective role by inhibiting phosphorylation of the m-TOR-ULK1 pathway and regulating autophagy.CNS neuroscience & therapeutics · 2021Article
- Ketamine Induces Lasting Antidepressant Effects by Modulating the NMDAR/CaMKII-Mediated Synaptic Plasticity of the Hippocampal Dentate Gyrus in Depressive Stroke Model.Neural plasticity · 2021Article
- Which Hyperglycemic Model of Zebrafish (Frontiers in cell and developmental biology · 2021Review
- PEBP1 acts as a rheostat between prosurvival autophagy and ferroptotic death in asthmatic epithelial cells.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Type 2 diabetes mellitus is characterized by insulin resistance. However, the complete molecular mechanism remains unclear. In this study, zebrafish were fed a long-term high-fat diet to induce type 2 diabetes, which resulted in a higher body weight, body mass index, more lipid vacuoles in liver, increased insulin transcription level in liver, brain and muscle, and high fasting blood glucose in the high-fat diet zebrafish. Oppositely, the transcription levels of insulin substrate-2 and glucose transporter 2 were significantly decreased, indicating insulin signaling pathway and glucose transport impaired in the insulin-targeting tissues. Transcription of the autophagy-related genes, ATG3, ATG4B, ATG5, ATG7, ATG12, and FOXO3, were decreased but autophagy inhibitor gene m-TOR increased, and autophagy-flux was inhibited in liver of the high-fat diet zebrafish. Main of these changes were confirmed in palmitic acid-treated HepG2 cells. Further, in co-immunoprecipitation and subcellular co-localization experiments, the conjunction of preproinsulin with cargo-recognition protein p62 increased, but conjuncts of autophagosome with p62-cargo, lysosomes with p62-cargo, and autolysosomes decreased apparently. Interestingly, lysosomes, autolysosomes and conjuncts of p62-insulin localized at the periphery of palmitic acid-treated cells, the margination of lysosomes may mediate deactivation of proteases activity. These findings suggest that intracellular high-lipid may trigger defective autophagy, defective downstream signaling of insulin and accumulated intracellular preproinsulin, leading to dysregulation of cell homeostasis mechanism, which may be one of reasons involved in insulin-resistance in type 2 diabetes.
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