Substrate competition and insulin action in animal models

increased basal plasma FFA and lactate concentrations are often present in obesity and may deeply affect insulin action. The inhibition of glucose tra nsport or phosphorylation is thought to be involved in this phenomenon, but the molecular mechanisms on the basis are still unknown. In our laboratory we observed that a chronic infusion of Intralipid plus heparin in rats sig nificantly decreased the insulin dependent-glucose uptake, as well as GLUT4 gene expression in muscular tissue. On the other hand it has been shown th at an enhanced plasma lactate concentration may increase insulin secretion and hepatic insulin clearance. Moreover we observed that chronic hyperlacta temia in rats is able to decrease glucose uptake in muscles, while reducing GLUT4 mRNA and protein in the same tissues. In obesity, lactate and FFA ov erproduction from visceral fat may therefore play a synergic role in reduci ng insulin sensitivity.