Downregulating SOCS3 with siRNA ameliorates insulin signaling and glucose metabolism in hepatocytes of IUGR rats with catch-up growth

作者：Ye, Juan; Zheng, Ruidan; Wang, Qun; Liao, Lihong; Ying, Yanqin; Lu, Huiling; Cianflone, Katherine; Ning, Qin; Luo, Xiaoping^*

来源：Pediatric Research, 2012, 72(6): 550-559.

DOI：10.1038/pr.2012.123

• FOR-GESTATIONAL-AGE
• ADIPOSE-TISSUE
• RESISTANCE
• RESTRICTION
• SUPPRESSOR
• PROTEINS
• LIVER
• SENSITIVITY
• INHIBITION
• ORIGINS

BACKGROUND: Individuals with intrauterine growth retardation (IUGR) who demonstrate a catch-up in body weight are prone to insulin resistance. High expressions of suppressor of cytokine signaling 3 (SOCS3) are thought to aggravate insulin resistance. We hypothesized that downregulating SOCS3 expression via small interfering RNA (siRNA) might have beneficial effects on insulin-resistant hepatocytes of catch-up growth IUGR rats (CG-IUGRs). @@@ METHODS: An IUGR rat model was employed via maternal nutritional restriction. After evaluating metabolic states of CG-IUGR offspring, effective SOCS3-specific siRNA (siSOCS3) was transfected into cultured hepatocytes using liposomes. mRNA levels of SOCS3, insulin receptor substrates (IRSs), phosphatidylinositol 3-kinase (PI3K), and Akt2, key gluconeogenesis genes, were assessed via real-time PCR. Protein expression and phosphorylation changes were evaluated via western blot. @@@ RESULTS: CG-IUGR hepatocytes showed increases in SOCS3 and gluconeogenic gene expressions, and decreases in IRS1 and PI3K expressions as compared with controls. After transfecting CG-IUGR hepatocytes with siSOCS3, protein levels of IRS1, PI3K, and phosphorylated Akt2 were higher as compared with those of untransfected CG-IUGR cells. Transcriptional suppression effects of gluconeogenesis genes were more obvious in siSOCS3-treated cells after insulin stimulation. @@@ CONCLUSION: Additional insights were provided to understand mechanisms of insulin resistance in CG-IUGR rats. Down-regulating SOCS3 might improve insulin signaling transduction and ameliorate hepatic glucose metabolism in insulin-resistant CG-IUGR rats in vitro.

• 出版日期2012-12
• 单位华中科技大学