title: The influence of down-regulation of suppressor of cellular signaling proteins by RNAi on glucose transport of intrauterine growth retardation rats.
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.
authors.affiliation: Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Liao
authors.forename: Ruidan
authors.initials: R
authors.lastname: Zheng
authors.forename: Chengbin
authors.initials: C
authors.lastname: Wang
authors.forename: Jinzhi
authors.initials: J
authors.lastname: Gao
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Ying
authors.forename: Qin
authors.initials: Q
authors.lastname: Ning
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Luo
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism; D011247:Pregnancy; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D051275:Glucose Transporter Type 4; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; C495694:Slc2a4 protein, rat; C491589:Socs1 protein, rat; C491410:Socs3 protein, rat; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose