Reduction of PTP1B by RNAi upregulates the activity of insulin controlled fatty acid synthase promoter.
Metabolic deregulation accompanying type II diabetes is characterized by insulin resistance in peripheral tissues (liver, muscle, and adipose), mediated by impairments in insulin receptor (IR) signaling. Protein tyrosine phosphatase 1B (PTP1B) has been shown to be a negative regulator of IR autophosphorylation and thus has been considered as a major therapeutic target for the treatment of type II diabetes. We use RNA interference technique to downregulate PTP1B expression in hepatoma cell line. A secretory HBV s-antigen was introduced as reporter and driven by mouse fatty acid synthase promoter, which is positively controlled by insulin signaling. Liver-targeted hydrodynamic injection in tail vein was introduced to transfer siRNA (or siRNA expression vector) and reporter plasmid into mouse liver. On fasted/refed and glucose stimulation condition, the HBV s-antigen in sera in RNAi group was higher than that in the negative group. Our results provided evidence that upregulation of insulin signaling by reducing PTP1B liver with RNAi can be a potent diabetes treatment method.
Xu
Jianfeng
J
Department of Biochemistry, School of Life Sciences, Fudan University, Shanghai 200433, China.
Li
Lin
L
Qian
Zhikang
Z
Hong
Jie
J
Shen
Shuiyuan
S
Huang
Weida
W
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D005227:Fatty Acids / Q000096:biosynthesis*; D005786:Gene Expression Regulation / Q000235:genetics; D007328:Insulin / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic / Q000378:metabolism; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000172:deficiency* / Q000235:genetics*; D034622:RNA Interference; D015398:Signal Transduction / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
D005227:Fatty Acids; D007328:Insulin; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; C516609:Ptpn1 protein, mouse