Abstract
Intrauterine growth retardation (IUGR) has been linked to metabolic syndrome including insulin resistance, and overexpression of suppressors of cytokine signaling (SOCSs) proteins is thought to be associated with increased whole-body insulin sensitivity. The insulin-resistant IUGR rat model was established by maternal food restriction (about 30% of the normal rats). The weight, length, and homeostasis model assessment of insulin resistance (HOMA-IR) of IUGR-born rats was higher than the control group. Insulin receptor substrate (IRS)-1 expression decreased, whereas SOCS-1 and SOCS-3 increased in the skeletal muscle of IUGR rats compared with the control group. The recombination plasmids PGPU6/GFP/Neo-SOCS-1small hairpin RNA (shRNA) and PGPU6/GFP/Neo-SOCS-3shRNA were transfected into skeletal muscle cells, and the shRNAs efficiently inhibited the expression of SOCS-1 and SOCS-3. Insulin-stimulated glucose transporter-4 (GLUT4) translocation was also dramatically increased. In conclusion, these data provide additional information on the mechanism of insulin resistance associated with IUGR. Down-regulation of SOCS-1 and SOCS-3 ameliorates the capacity of glucose transport and provides a potential gene therapy approach to managing metabolic syndrome.
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Abbreviations
- GLUT:
-
glucose transporter
- HOMA-IR:
-
homeostasis model assessment of insulin resistance
- IRS-1:
-
insulin receptor substrate-1
- SOCS:
-
suppressors of cytokine signaling
- shRNA:
-
small hairpin RNAs
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Supported by the National Natural Science Foundation of China (No.30672262 and No.30772358) [X.L.], Eleventh Five-year National Science Supported Planning Project (No.2006BAI05A07) [X.L.], the Doctor Program of Higher Education from the Ministry of Education of China (No. 20060487062) [X.L.], and the 973 National Basic Research Project from the Ministry of Science and Technology of China (No. 2007CB512900) [Q.N.].
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Liao, L., Zheng, R., Wang, C. et al. The Influence of Down-Regulation of Suppressor of Cellular Signaling Proteins by RNAi on Glucose Transport of Intrauterine Growth Retardation Rats. Pediatr Res 69, 497–503 (2011). https://doi.org/10.1203/PDR.0b013e31821769bd
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DOI: https://doi.org/10.1203/PDR.0b013e31821769bd
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