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
| Autor: | Anna Planavila, Mireia Jové, Manuel Vázquez-Carrera, Juan C. Laguna |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
medicine.medical_specialty
Monosaccharide Transport Proteins Palmitates Down-Regulation Muscle Proteins Inflammation Biology Ceramides Cell Line Mice chemistry.chemical_compound Endocrinology Insulin resistance Pyrrolidine dithiocarbamate Internal medicine medicine Animals Calphostin RNA Messenger Extracellular Signal-Regulated MAP Kinases Muscle Skeletal Protein kinase A Protein Kinase C Protein kinase C Glucose Transporter Type 4 Interleukin-6 NF-kappa B Glucose transporter Skeletal muscle medicine.disease Enzyme Activation medicine.anatomical_structure chemistry Mitogen-Activated Protein Kinases medicine.symptom |
| Zdroj: | Endocrinology. 146:3087-3095 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2004-1560 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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