Full-length adiponectin attenuates insulin signaling and inhibits insulin-stimulated amino Acid transport in human primary trophoblast cells.
Full-length adiponectin attenuates insulin signaling and inhibits insulin-stimulated amino Acid transport in human primary trophoblast cells.
复制标题
作者：
Jones HN;Jansson T;Powell TL
肥胖和妊娠糖尿病导致母体脂联素水平降低，胎盘营养转运蛋白上调；然而，脂联素对胎盘功能的影响尚不清楚。我们假设脂联素调节胎盘氨基酸运输。用球状脂联素（gAd）或全长脂联素（fAd）单独或与胰岛素联合培养人原代滋养细胞。检测系统A和L氨基酸转运以及SNAT1、SNAT2和SNAT4异构体表达。测定amp活化蛋白激酶（AMPK）、磷脂酰肌醇3激酶- akt和过氧化物酶体增殖物活化受体-α (PPARα)信号通路的活性。在缺乏胰岛素的情况下，gAd刺激AMPK Thr172磷酸化、SNAT2蛋白表达和系统A活性。这种作用似乎是由白细胞介素-6的释放和转录的信号转换器和激活因子3 （STAT3）信号传导介导的，因为在STAT3被小干扰RNA沉默的细胞中，gAd不能刺激系统A。单独的fAd对系统A活性和SNAT表达没有影响。胰岛素增加AKT和胰岛素受体底物1 （IRS-1）磷酸化、系统A活性和SNAT2表达。当与胰岛素联合使用时，gAd不影响系统A活性或SNAT表达。相反，fAd消除了胰岛素刺激的AKT Thr308和IRS-1 Tyr612磷酸化、system A活性和SNAT2表达。此外，fAd增加了PPARα的表达和PPARα (Ser21)的磷酸化。与文献报道的脂联素在肝脏和肌肉中的胰岛素增敏作用相反，fAd减弱了人原代滋养细胞中的胰岛素信号。因此，fAd抑制胰岛素刺激的氨基酸运输，这可能对胎盘营养物质运输和胎儿生长在与母体脂联素水平改变相关的妊娠并发症中具有重要意义。
Maternal adiponectin levels are reduced and placental nutrient transporters are upregulated in obesity and gestational diabetes mellitus; however, the effects of adiponectin on placental function are unknown. We hypothesized that adiponectin regulates placental amino acid transport. Human primary trophoblast cells were cultured and incubated with globular adiponectin (gAd) or full-length adiponectin (fAd) alone or in combination with insulin. System A and L amino acid transport and SNAT1, SNAT2, and SNAT4 isoform expression was measured. The activity of the AMP-activated protein kinase (AMPK), phosphatidylinositol 3 kinase–AKT, and peroxisome proliferator–activated receptor-α (PPARα) signaling pathways was determined. In the absence of insulin, gAd stimulated AMPK Thr172 phosphorylation, SNAT2 protein expression, and system A activity. This effect appeared to be mediated by interleukin-6 release and signal transducer and activator of transcription 3 (STAT3) signaling because gAd failed to stimulate system A in cells in which STAT3 had been silenced using small interfering RNA. fAd alone had no effect on system A activity or SNAT expression. Insulin increased AKT and insulin receptor substrate 1 (IRS-1) phosphorylation, system A activity, and SNAT2 expression. When combined with insulin, gAd did not affect system A activity or SNAT expression. In contrast, fAd abolished insulin-stimulated AKT Thr308 and IRS-1 Tyr612 phosphorylation, system A activity, and SNAT2 expression. Furthermore, fAd increased PPARα expression and PPARα (Ser21) phosphorylation. In contrast to the insulin-sensitizing actions of adiponectin in liver and muscle reported in the literature, fAd attenuates insulin signaling in primary human trophoblast cells. As a result, fAd inhibits insulin-stimulated amino acid transport, which may have important implications for placental nutrient transport and fetal growth in pregnancy complications associated with altered maternal adiponectin levels.
登录
查看更多内容
脂联素诱导的白介素-6（IL-6），单核细胞趋化蛋白-1（MCP-1，CCL2）和白介素8（IL-8，CXCL8）的分泌受到I型糖尿病患者的单核细胞的损害。
影响因子：
9.3
作者：
Abke, Sabine;Neumeier, Markus;Weigert, Johanna;Wehrwein, Gabriele;Eggenhofer, Elke;Schaeffler, Andreas;Maier, Kevin;Aslanidis, Charalampos;Schoelmerich, Juergen;Buechler, Christa
通讯作者：
Buechler, Christa
影响因子：
8
作者：
Boney, CM;Verma, A;Vohr, BR
通讯作者：
Vohr, BR
影响因子：
8.2
作者：
Chen, J;Tan, B;Randeva, HS
通讯作者：
Randeva, HS
影响因子：
82.9
作者：
Berg, AH;Combs, TP;Scherer, PE
通讯作者：
Scherer, PE
影响因子：
5.8
作者：
Caminos, JE;Nogueiras, R;Diéguez, C
通讯作者：
Diéguez, C