Externally liberated NE has been shown to have a profound effect on neighboring tissues in cancer cells, where its uptake led to the degradation of IRS1, thereby uncoupling the PI3K pathway from the negative regulatory effect of IRS1, thereby leading to uncontrolled growth (36). In a similar manner, exogenous NE was shown to interact with hepatocytes in a murine model for diabetes, where it also enzymatically degraded IRS1 (37), thereby promoting glucose intolerance. For this reason, we examined the influence of exogenous NE on BeWo cells. First, the optimal incubation period of NE with BeWo was determined by monitoring cell viability by means of a MTT assay. Influence of NE on BeWo indicated that akin to the report on cancer cells (36), exogenous NE leads to a significant degradation of IRS1 protein (Figure 4D). This effect of NE is also evident in cultures treated with insulin (Figure 4D). The decrease in IRS1 protein levels was associated with a concomitant decrease in glucose transporter type 4 gene (GLUT4), resulting in diminished glucose uptake (Figure 4E). Once again, this effect was also present in insulin-treated cultures, albeit to a lower level than cultures without insulin (Figure 4E).