In pancreatic α-cells, XBP1 knockdown causes insulin resistance via the phosphorylation of both IRE1α and JNK, and decreases the expression of glucagon genes via the downregulation of FOXO1, a key factor in the insulin/insulin-like growth factor 1 pathway, which can bind to the promoter of the preproglucagon genes [127]. Here, ERN1 is linked to Insulin resistance.