Tsuchiya Ayako, Kanno Takeshi, Nishizaki Tomoyuki
Cell Physiol Biochem. 2013;32(5):1451-9. doi: 10.1159/000356582.
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.
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.
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.
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.
背景/目的：游离脂肪酸（FFA）参与多种信号转导途径。本研究调查了饱和脂肪酸硬脂酸对蛋白酪氨酸磷酸酶1B（PTP1B）活性、Akt活性以及与胰岛素信号相关的细胞葡萄糖摄取的影响。
在无细胞条件下测定PTP1B活性。在分化的3T3-L1-GLUT4myc脂肪细胞中监测胰岛素受体和Akt的磷酸化以及细胞对葡萄糖的摄取。
在无细胞PTP1B测定中，硬脂酸以浓度（1-30μM）依赖性方式抑制PTP1B活性。对于3T3-L1-GLUT4myc脂肪细胞，胰岛素以浓度（100 fM-100 nM）依赖性方式使胰岛素受体的Tyr1185位点和Akt的Thr308及Ser473位点磷酸化，并以浓度（0.1-100 nM）依赖性方式刺激细胞对葡萄糖的摄取。硬脂酸（30μM）显著增加胰岛素诱导的胰岛素受体Tyr1185位点的磷酸化，但胰岛素诱导的Akt磷酸化未显著增强。硬脂酸（30μM）自身可促进脂肪细胞对葡萄糖的摄取。
本研究结果表明，硬脂酸是一种有效的PTP1B抑制剂，可能会增强胰岛素受体信号传导，从而刺激脂肪细胞摄取葡萄糖。
