1. [LRP16 gene causes insulin resistance in C2-C12 cells by inhibiting the IRS-1 signaling and the transcriptional activity of peroxisome proliferator actived receptor γ]
- Author
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Li, Zang, Yi-ming, Mu, Zhao-hui, Lü, Bing, Xue, Xiao-li, Ma, Guo-qing, Yang, Jian-ming, Ba, Jing-tao, Dou, and Ju-ming, Lu
- Subjects
Myoblasts ,PPAR gamma ,Mice ,Insulin Receptor Substrate Proteins ,Animals ,Insulin ,Insulin Resistance ,Carrier Proteins ,Receptor, Insulin ,Cell Line ,Neoplasm Proteins ,Signal Transduction - Abstract
To explore the effect of LRP (leukemia related protein) 16 on insulin resistance in C2-C12 cells and explore its molecular mechanism.Lipidosome transfection and lentivirus mediated siRNA (small interfering RNA) technology were used to establish LRP 16 overexpression and underexpression cell lines and their corresponding control cell lines. And 2-deoxy-[(3)H]-glucose was used to measure the effect of LRP 16 on insulin-stimulated glucose uptake. The effects of LRP16 on the phosphorylation of IRS (insulin receptor substrate)-1, Akt and the expressions of PI3K (p85), PPAR (peroxisome proliferator actived receptor) γ and GLUT-4 were detected by Western blot. Luciferase was used to study the effect of LRP16 on the transcriptional activity of PPARγ.Insulin-stimulated glucose uptake decreased to 46% of the control when LRP16 was over-expressed [(4700 ± 97) vs. (10200 ± 347), P0.01]. And the insulin-stimulated glucose uptake was 1.73 fold of control when the expression of LRP16 was suppressed in C2-C12 cells [(17600 ± 466) vs (10200 ± 91), P0.05]. The overexpression of LRP16 attenuated the insulin-induced tyrosine phosphorylation of IRS-1, the phosphorylation of Akt and the expressions of PI3K (p85), PPARγ and GLUT-4. But it promoted the insulin-induced phosphorylation of IRS-1 at Ser307 in C2-C12 cells. LRP16 decreased the transcriptional activity of PPARγ in a dose-dependent manner. The transcriptional activity of PPARγ decreased to 43% and 27% of the control when the doses of pcDNA3.1-16 were 0.4 µg and 0.5 µg [(76 ± 11) vs (33 ± 9), P0.01] and 27% [(21 ± 9) vs (76 ± 11), P0.01].LRP16 gene causes insulin resistance in C2-C12 cells by inhibiting the IRS-1 signaling and the transcriptional activity of PPARγ.
- Published
- 2011