INS and Insulin resistance: Increased FFA flux from adipose tissue to non-adipose tissue reduces the expression of insulin receptor substrate 1 (IRS-1), impairs the activation of phosphoinositide 3-kinase/protein kinase B (PI3K–AKT) signaling in the liver and skeletal muscles, and inhibits GLUT4 translocation to the cell membrane, down-regulating insulin signaling and causing insulin resistance [18].