JNK, upregulated in insulin-responsive tissues including the liver, adipose tissue, and skeletal muscle of T2D patients, phosphorylates insulin receptor substrate 1/2 (IRS-1/2) on serine residues, thereby disrupting downstream phosphatidylinositol 3-kinase (PI3K)/serine threonine kinase (Akt) signaling [104]. This evidence concerns the gene INS and type 2 diabetes mellitus.