Stearic acid serves as a potent inhibitor of protein tyrosine phosphatase 1B.

BACKGROUND/AIMS Free fatty acids (FFAs) are implicated in diverse signal transduction pathways. The present study investigated the effects of the saturated FFA stearic acid on protein tyrosine phosphatase 1B (PTP1B) activity, Akt activity, and glucose uptake into cells relevant to insulin signal. METHODS PTP1B activity was assayed under the cell-free conditions. Phosphorylation of insulin receptor and Akt and glucose uptake into cells were monitored in differentiated 3T3-L1-GLUT4myc adipocytes. RESULTS In the cell-free PTP1B assay, stearic acid suppressed PTP1B activity in a concentration (1-30 μM)-dependent manner. For 3T3-L1- GLUT4myc adipocytes insulin phosphorylated insulin receptor at Tyr1185 and Akt at Thr308 and Ser473 in a concentration (100 fM-100 nM)-dependent manner and stimulated glucose uptake into cells in a concentration (0.1-100 nM)-dependent manner. Stearic acid (30 μM) significantly increased insulin-induced phosphorylation of insulin receptor at Tyr1185, but insulin-induced phosphorylation of Akt was not significantly enhanced. Stearic acid (30 μM) by itself promoted glucose uptake into adipocytes. CONCLUSION The results of the present study indicate that stearic acid serves as a potent PTP1B inhibitor, possibly causing an enhancement in the insulin receptor signaling to stimulate glucose uptake into adipocytes.