Cited by 133Adipokines, Inflammation, and Metabolic DiseasesMetabolism, Diabetes, and CancerAdipose Tissue and Metabolism

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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

Jové, Mireia, Planavila, Anna, Laguna, Juan Carlos, Vázquez-Carrera, Manuel·2005·Endocrinology

DOI 10.1210/en.2004-1560

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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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Authors: Jové, M., Planavila, A., Laguna, J. C., & Vázquez-Carrera, M.
Affiliations: Universitat de Barcelona (ES)
ORCID: Planavila, Anna
Laguna, Juan Carlos
Venue: Endocrinology
Publisher: The Endocrine Society
Published: 2005-07-01
Volume: 146
Issue: 7
Pages: 3087-3095
ISSN: 0013-7227 (ISSN-L)
1945-7170
DOI: 10.1210/en.2004-1560
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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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

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