Figure 2: RA synergizes with insulin to induce Gck expression and attenuates insulin-suppressed Pck1 expression. RA induces the expression levels of Gck and Pck1 via the activation of both RAR/RXR (the oval dimmers on the RAREs) in the absence of insulin. Insulin alone stimulates the expression of Gck and suppresses the expression of Pck1. In the presence of both insulin and RA, the expression of Gck is further increased (synergy). On the other hand, the insulin-mediated suppression of Pck1 expression is attenuated. This is because RA still induces Pck1 expression via activation of RAR in the presence of insulin. Therefore, Pck1 transcript level in the RA + insulin group is higher than that in the insulin group (attenuation).