Effects of small interference RNA against PTP1B and TCPTP on insulin signaling pathway in mouse liver: evidence for non-synergetic cooperation.

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. Two closely-related protein tyrosine phosphatases, PTP1B and TCPTP both showed abilities to negatively regulate insulin receptor signaling. In order to test whether these two phosphatases can act synergistically, hydrodynamic injection was applied to deliver small interfering RNA (siRNA) of PTP1B and/or TCPTP to mouse liver. By measuring insulin-sensitive reporter gene expression and plasma glucose of diabetic mice, we found siRNA of PTP1B or TCPTP alone can sensitize insulin signal transduction, but combined treatment of both siRNAs had no better effects than siRNA of PTP1B. These results suggested siRNA of PTP1B and TCPTP can strengthen insulin signaling, but their effects do not appear to be synergistic in mouse liver.