Role of tumor suppressor PTEN in tumor necrosis factor alpha-induced inhibition of insulin signaling in murine skeletal muscle C2C12 cells
| Autor: | Tzeng Tf, I-Min Liu, Lo Yt |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
medicine.medical_specialty
Endocrinology Diabetes and Metabolism Clinical Biochemistry Muscle Fibers Skeletal Biochemistry Cell Line Mice Phosphatidylinositol 3-Kinases Endocrinology Internal medicine medicine Tensin PTEN Animals Insulin RNA Messenger Protein kinase B Glucose Transporter Type 4 biology Tumor Necrosis Factor-alpha Tumor Suppressor Proteins Biochemistry (medical) PTEN Phosphohydrolase Skeletal muscle General Medicine Oligonucleotides Antisense Insulin receptor medicine.anatomical_structure Glucose Gene Expression Regulation biology.protein Phosphorylation Tumor necrosis factor alpha Signal transduction Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 39(3) |
| ISSN: | 0018-5043 |
| Popis: | In an attempt to clarify the role of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) in muscle insulin resistance, we investigated the effect of PTEN on phosphoinositide 3 (PI3)-kinase/Akt related insulin signaling pathway in skeletal muscle-like C 2 C 12 cells damaged by tumor necrosis factor-alpha (TNFα). C 2 C 12 cells cultured with TNFα (10 ng/ml) for 1 h displayed a marked decrease of insulin-stimulated 2-[ 14 C]-deoxy- D-glucose (2-DG) uptake in parallel with an elevation of PTEN mRNA and protein levels. However, pretreatment of PTEN antisense oligonucleotide (AS) (1 μmol/l for 3 days) for specific inhibition of PTEN expression in C 2 C 12 cells abolished the TNFα-induced changes in 2-DG uptake. Similar pretreatment with PTEN AS, but not with sense oligonucleotide (1 μmol/l for 3 days), eliminated the ability of TNFα to impair insulin-stimulated signals including p85 regulatory subunit of PI3-kinase expression and the degree of Akt serine phosphorylation as well as protein expression in glucose transporter subtype 4. Data taken from cultured C 2 C 12 cells emphasize the negative regulatory of muscle PI3-kinase/Akt signaling pathways as the major substrate of PTEN but also support the concept that PTEN contributes to the development of insulin resistance in skeletal muscle. |
| Databáze: | OpenAIRE |
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