The inhibitory action of free fatty acids on glucose transport, oxidation, and glycogen synthesis may be responsible for lipid-induced insulin resistance in humans.

This study investigated the mechanism of action of lipid-induced insulin resistance in humans. Researchers measured the skeletal muscle glycogen levels, plasma levels of free fatty acids, and serum glucose-6-phosphate concentrations in nine healthy subjects at intervals of 15 minutes for 6 hours.

They discovered that high plasma concentration of free fatty acids inhibited glucose uptake and increased insulin resistance by cells of the skeletal muscle, therefore increasing the risk of type 2 diabetes development. According to this study, the inhibition of glucose transport followed by a drastic reduction in glycogen synthesis and glucose oxidation mediated the insulin resistance activity of free fatty acids .