The DOI matches its Crossref record; 47 of the 49 references it cites were found in a registry or an index.
Palmitate-Induced Interleukin 6 Production Is Mediated by Protein Kinase C and Nuclear-Factor κB Activation and Leads to Glucose Transporter 4 Down-Regulation in Skeletal Muscle Cells
Abstract
The mechanisms by which elevated levels of free fatty acids cause insulin resistance are not well understood. In addition, accumulating evidence suggests a link between inflammation and type 2 diabetes. Here, we report that exposure of C2C12 skeletal muscle cells to 0.5 mm palmitate results in increased mRNA levels (3.5-fold induction; P < 0.05) and secretion (control 375 ± 57 vs. palmitate 1129 ± 177 pg/ml; P < 0.001) of the proinflammatory cytokine IL-6. Palmitate increased nuclear factor-κB activation and coincubation of the cells with palmitate and the nuclear factor-κB inhibitor pyrrolidine dithiocarbamate prevented both IL-6 expression and secretion. Furthermore, incubation of palmitate-treated cells with calphostin C, a strong and specific inhibitor of protein kinase C, and phorbol myristate acetate, that down-regulates protein kinase C in long-term incubations, abolished induction of IL-6 production. Finally, exposure of skeletal muscle cells to palmitate caused a fall in the mRNA levels of glucose transporter 4 and insulin-stimulated glucose uptake, whereas in the presence of anti-IL-6 antibody, which neutralizes the biological activity of mouse IL-6 in cell culture, these reductions were prevented. These findings suggest that IL-6 may mediate several of the prodiabetic effects of palmitate.
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“The actions of these stimuli serve to not only further induce tissue expression and secretion of IL-6 and TNFα (via the NFκB pathway, [3, 4]), but impair control of numerous signalling pathways regulating skeletal muscle insulin signalling, glucose uptake, mitochondrial fuel oxidation and respiration that impact negatively upon skeletal muscle energy homeostasis [2, 5–7].”
From Proinflammatory NFkB signalling promotes mitochondrial dysfunction in skeletal muscle in response to cellular fuel overloading (2019) · cites this paper as [3]
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Research works printed but not linked: 1
- Senn, 2002, Suppressor of cytokine signaling-3 (SOCS-3) is a potential mediator of interleukin-6 dependent insulin resistance, Diabetes, 51, A324
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Kim, J.-A., Montagnani, M., Koh, K. K., & Quon, M. J. (2006) · Circulation · doi:10.1161/circulationaha.105.563213 · Cited by 1,652
Cardiovascular Actions of Insulin
Muniyappa, R., Montagnani, M., Koh, K. K., & Quon, M. J. (2007) · Endocrine Reviews · doi:10.1210/er.2007-0006 · Cited by 888
Kennedy, A. J., Martinez, K., Chuang, C., LaPoint, K., & McIntosh, M. (2008) · Journal of Nutrition · doi:10.3945/jn.108.098269 · Cited by 579
Oleate Reverses Palmitate-induced Insulin Resistance and Inflammation in Skeletal Muscle Cells
Coll, T., Eyre, E., Rodríguez-Calvo, R., Palomer, X., Sánchez, R. M., Merlos, M., Laguna, J. C., & Vázquez-Carrera, M. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m708700200 · Cited by 347
Self-citationRenin-angiotensin-aldosterone system and oxidative stress in cardiovascular insulin resistance
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Metadata
- Authors
- Jové, M., Planavila, A., Laguna, J. C., & Vázquez-Carrera, M.
- Affiliations
- Universitat de Barcelona (ES)
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2005-07-01
- Volume
- 146
- Issue
- 7
- Pages
- 3087-3095
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2130177297
- Cited by
- 133
- References
- 49
- Citations by year
- 2025: 1 · 2024: 4 · 2022: 5 · 2021: 3 · 2020: 2 · 2019: 4 · 2018: 5 · 2017: 2 · 2016: 4 · 2015: 8 · 2014: 7 · 2013: 14 · 2012: 11
- FWCI
- 7.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Universitat de Barcelona
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- palmitate, interleukin-6, protein kinase C, NF-κB activation, glucose transporter 4, skeletal muscle cells, insulin resistance, free fatty acids, inflammation, type 2 diabetes, insulin-stimulated glucose uptake, pyrrolidine dithiocarbamate, calphostin C, phorbol myristate acetate
- MeSH terms
- Animals, Cell Line, Ceramides, Enzyme Activation, Monosaccharide Transport Proteins, Muscle Proteins, Palmitates, Protein Kinase C, RNA, Messenger, Down-Regulation, Interleukin-6, NF-kappa B, Muscle, Skeletal, Mitogen-Activated Protein Kinases, Extracellular Signal-Regulated MAP Kinases, Glucose Transporter Type 4, Mice
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