Figure 2 Mechanisms for free fatty acid (FFA)‐induced skeletal muscle insulin resistance. (A) Normal glucose uptake into skeletal muscle occurs via binding of insulin to the insulin receptor, resulting in receptor autophosporylation and subsequent binding and tyrosine phosporylation of insulin receptor substrate (IRS)‐1. Subsequently, phosphatidylinositol 3‐kinase (PI3K) is activated and results in downstream activation of Akt, leading to GLUT‐4 translocation to the myocyte plasma membrane and glucose uptake into the cell. (B) Increased intramyocellular lipid content leads to the activation of protein kinase Cθ (PKCθ) which results in serine phosporylation of IRS‐1, thereby inhibiting its tyrosine phosphorylation. This prevents the activation of PI3K and GLUT‐4 translocation to the cell surface. Thus glucose entry into the cell is inhibited. AMPK, AMP‐activated protein kinase; DAG, diacylglycerol.