Oleic acid stimulates glucose uptake into adipocytes by enhancing insulin receptor signaling

The present study investigated cis-unsaturated free fatty acid (ffa)-regulated glucose uptake. in the cell-free assay of protein tyrosine phosphatase 1b (ptp1b),cis-unsaturated ffas such as linoleic,linolenic,and oleic acid significantly suppressed ptp1b activity in a concentration (1 - 100 μm)-dependent manner,with the highest potential for oleic acid. oleic acid (1 μm) stimulated insulin (0.1 nm)-induced phosphorylation of the insulin receptor at tyr1185 and increased insulin (0.1 nm)-induced phosphorylation of akt at thr308 and ser473 in differentiated 3t3-l1-glut4myc adipocytes. in the föerster resonance energy transfer analysis,oleic acid activated rac1 in pc-12 cells,which is inhibited by the phosphatidylinositol 3-kinase (pi3k) inhibitor wortmannin,the 3-phosphoinositide-dependent protein kinase-1 (pdk1) inhibitor bx912,or the akt inhibitor mk2206. oleic acid (1 μm) significantly increased insulin (0.1 nm)-stimulated glucose uptake in 3t3-l1-glut4myc adipocytes,although oleic acid by itself had no effect on the glucose uptake. taken together,the results of the present study show that oleic acid enhances insulin receptor signaling through a pathway along an insulin receptor/pi3k/pdk1/akt/rac1 axis in association with ptp1b inhibition and facilitates insulin-induced glucose uptake into adipocytes. © 2015 the japanese pharmacological society.