INS and Hyperglycemia: In the adipose tissue, insulin resistance increases lipolysis and NEFA influx to the liver, muscle, and vascular endothelium (lipotoxicity) and stimulates the release of pro-inflammatory cytokines leading to impairment of insulin signaling in these tissues; these effects aggravate oxidative stress and hyperglycemia (see “Contribution of Individual Tissues to Insulin Resistance”) (Fig. 3).