ArticleDiabetologia2010
Glucosamine-induced endoplasmic reticulum stress affects GLUT4 expression via activating transcription factor 6 in rat and human skeletal muscle cells.
Article in Diabetologia, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 67 citations in OpenAlex.
- RNF186 controls glucose metabolism in metabolic dysfunction-associated fatty liver disease.Cell & bioscience · 2025Article
- Single-cell transcriptomic profiling reveals cell type heterogeneity between HFpEF and HFrEF.Communications biology · 2025Article
- Sucrose-induced metabolic syndrome differentially affects energy metabolism and fiber phenotype of EDL and soleus muscles during exercise in the rat.Physiological reports · 2024Article
- The activation of spliced X-box binding protein 1 by isorhynchophylline therapy improves diabetic encephalopathy.Cell biology and toxicology · 2023Article
- Review
- Circadian Clock Desynchronization and Insulin Resistance.International journal of environmental research and public health · 2022Review
- Hidden Agenda - The Involvement of Endoplasmic Reticulum Stress and Unfolded Protein Response in Inflammation-Induced Muscle Wasting.Frontiers in immunology · 2022Review
- Review
- Glucose transporters in adipose tissue, liver, and skeletal muscle in metabolic health and disease.Pflugers Archiv : European journal of physiology · 2020Review
- Article
- Understanding the Role of Exercise in Nonalcoholic Fatty Liver Disease: ERS-Linked Molecular Pathways.Mediators of inflammation · 2020Review
- Review
- Percutaneous muscle biopsy-induced tissue injury causes local endoplasmic reticulum stress.Physiological reports · 2018Article
- Citrus aurantium L. dry extracts promote C/ebpβ expression and improve adipocyte differentiation in 3T3-L1 cells.PloS one · 2018Article
- Specific CpG hyper-methylation leads to Ankrd26 gene down-regulation in white adipose tissue of a mouse model of diet-induced obesity.Scientific reports · 2017Article
- IL-15 expression increased in response to treadmill running and inhibited endoplasmic reticulum stress in skeletal muscle in rats.Endocrine · 2015Article
- Protein kinase R-like endoplasmic reticulum kinase and glycogen synthase kinase-3α/β regulate foam cell formation.Journal of lipid research · 2014Article
- Endoplasmic reticulum stress and oxidative stress in cell fate decision and human disease.Antioxidants & redox signaling · 2014Review
- The importance of the cellular stress response in the pathogenesis and treatment of type 2 diabetes.Cell stress & chaperones · 2014Article
- Using a large-scale knowledge database on reactions and regulations to propose key upstream regulators of various sets of molecules participating in cell metabolism.BMC systems biology · 2014Article
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
aims/hypothesisGlucosamine, generated during hyperglycaemia, causes insulin resistance in different cells. Here we sought to evaluate the possible role of endoplasmic reticulum (ER) stress in the induction of insulin resistance by glucosamine in skeletal muscle cells.
methodsReal-time RT-PCR analysis, 2-deoxy-D: -glucose (2-DG) uptake and western blot analysis were carried out in rat and human muscle cell lines.
resultsIn both rat and human myotubes, glucosamine treatment caused a significant increase in the expression of the ER stress markers immunoglobulin heavy chain-binding protein/glucose-regulated protein 78 kDa (BIP/GRP78 [also known as HSPA5]), X-box binding protein-1 (XBP1) and activating transcription factor 6 (ATF6). In addition, glucosamine impaired insulin-stimulated 2-DG uptake in both rat and human myotubes. Interestingly, pretreatment of both rat and human myotubes with the chemical chaperones 4-phenylbutyric acid (PBA) or tauroursodeoxycholic acid (TUDCA), completely prevented the effect of glucosamine on both ER stress induction and insulin-induced glucose uptake. In both rat and human myotubes, glucosamine treatment reduced mRNA and protein levels of the gene encoding GLUT4 and mRNA levels of the main regulators of the gene encoding GLUT4 (myocyte enhancer factor 2 a [MEF2A] and peroxisome proliferator-activated receptor-gamma coactivator 1alpha [PGC1alpha]). Again, PBA or TUDCA pretreatment prevented glucosamine-induced inhibition of GLUT4 (also known as SLC2A4), MEF2A and PGC1alpha (also known as PPARGC1A). Finally, we showed that overproduction of ATF6 is sufficient to inhibit the expression of genes GLUT4, MEF2A and PGC1alpha and that ATF6 silencing with a specific small interfering RNA is sufficient to completely prevent glucosamine-induced inhibition of GLUT4, MEF2A and PGC1alpha in skeletal muscle cells. CONCLUSIONS/
interpretationIn this work we show that glucosamine-induced ER stress causes insulin resistance in both human and rat myotubes and impairs GLUT4 production and insulin-induced glucose uptake via an ATF6-dependent decrease of the GLUT4 regulators MEF2A and PGC1alpha.
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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.