nck1 has been linked to glucose tolerance and insulin signaling within certain tissues, namely the liver, in obese mice. a deletion of the protein also causes a decrease of er stress signaling within these obese cells, which is normally increased by the excessive fat. this stress causes expression of the unfolded protein response pathway, which leads to a decrease in glucose tolerance and inactivation of insulin signaling in certain cell types. this renewed glucose tolerance and insulin signaling is caused by the inhibition of the unfolded protein response pathway, particularly the protein ire1alpha, and its subsequent phosphorylation of irs-1 that causes insulin signaling to be blocked. ire1alpha is involved with the jnk pathway that is responsible for the phosphorylation of irs-1. nck1 regulates the activation of ire1alpha within the pathway and when removed from the pathway disrupts activation. this means that nck1 has an interaction with the upr and that a deletion can cause a decrease in the stress pathway from the er in the mice. these deficient, obese mice also show increased insulin-induced phosphorylation of pkb within the liver but do not possess the same expression in adipose tissues or skeletal muscles. this evidence points to the pathway being er stress induced within liver tissue.