ANPEP and Insulin resistance: AMPK activated by APN can directly inhibit ribosomal protein S6 kinase 1 (S6K1); on the one hand, it reduces the risk of insulin resistance caused by increased phosphorylation of insulin receptor substrate-1 (IRS-1) in Ser636/639 [23], and, on the other hand, AMPK can also activate the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signal transduction pathway for insulin signal transmission and regulation of the glucose metabolism [22, 24].