The AT1 receptor autoantibody causes hypoglycemia in fetal rats via promoting the STT3A-GLUT1-glucose uptake axis in liver
The AT1 receptor autoantibody causes hypoglycemia in fetal rats via promoting the STT3A-GLUT1-glucose uptake axis in liver
复制标题
AT1受体自身抗体通过促进肝脏STT3A-GLUT1-葡萄糖摄取轴引起胎鼠低血糖
DOI：
10.1016/j.mce.2020.111022
复制
发表时间：
2020
影响因子：
4.1
通讯作者：
Huirong Liu
中科院分区：
文献类型：
--
作者：
Pengli Wang;Chunyu He;Mingming Yue;Tongtong Wang;Lina Bai;Ye Wu;Dan Liu;Meili Wang;Yan Sun;Yan Li;Suli Zhang;Huirong Liu
血糖对胎儿的发育和代谢平衡非常重要。妊娠期有害因素的刺激可引起血糖异常。血管紧张素Ⅱ 1型受体自身抗体（AT 1-AA）是一种新发现的妊娠期有害因子，可引起胎儿宫内生长受限和成人血糖紊乱。然而，AT 1-AA是否以及如何影响妊娠期胎儿的血糖水平尚不清楚。本研究的目的是观察AT 1-AA阳性孕鼠妊娠晚期的胎鼠血糖水平，并探讨肝脏葡萄糖转运蛋白在这一过程中的作用。我们通过将AT 1-AA注射到妊娠第二个三月的大鼠的尾静脉中来建立AT 1-AA阳性妊娠大鼠。尽管妊娠晚期胎儿血糖水平降低，但检测到肝脏葡萄糖摄取增加。通过分离膜蛋白和胞浆蛋白，我们证实了在胎肝细胞中负责葡萄糖转运的葡萄糖转运蛋白1（GLUT 1）的表达和膜转运率均上调，同时伴随着N-糖基转移酶STT 3A的表达增加，STT 3A有助于GLUT 1的N-糖基化。通过分离细胞膜蛋白和胞浆蛋白以及免疫荧光技术检测HepG 2细胞中GLUT 1的表达和膜转运率以及STT 3A的表达，从而降低培养液中的葡萄糖含量。GLUT 1抑制剂WZB 117逆转了AT 1-AA引起的培养基中葡萄糖含量的降低、葡萄糖摄取的增加、GLUT 1表达和膜转运率的增加。N-糖基转移酶抑制剂NGI以及si-STT 3A逆转了AT 1-AA诱导的STT 3A-GLUT 1-葡萄糖摄取效应的上调。这项研究表明，AT 1-AA通过肝脏中的STT 3A-GLUT 1-葡萄糖摄取轴降低胎儿的血糖水平。
Blood glucose is of great importance to development and metabolic homeostasis in fetuses. Stimulation of harmful factors during gestation induces pathoglycemia. Angiotensin II type 1 receptor autoantibody (AT1-AA), a newly discovered gestational harmful factor, has been shown to induce intrauterine growth restriction in fetuses and glucose disorders in adults. However, whether and how AT1-AA influences the blood glucose level of fetuses during gestation is not yet clear. The purpose of the current study was to observe the fetal blood glucose level of AT1-AA-positive pregnant rats during late pregnancy and to determine the roles that hepatic glucose transporters play in this process. We established AT1-AA-positive pregnant rats by injecting AT1-AA into the caudal veins of rats in the 2nd trimester of gestation. Although the fetal blood glucose level in the 3rd trimester of gestation decreased, hepatic glucose uptake increased detected. Through separating membrane and cytosolic proteins, we demonstrated that both the expression and membrane transport ratio of glucose transporter 1 (GLUT1), which is responsible for glucose transport in fetal hepatocytes, were upregulated, accompanied by increased expression of N-glycosyltransferase STT3A, which contributes to the N-glycosylation of GLUT1.In vitro, we identified that AT1-AA increased glucose uptake, the expression and membrane transport ratio of GLUT1 and the expression of STT3A in HepG2 cell lines via separating membrane and cytosolic proteins and immunofluorescence, resulting in the decreased glucose content in the medium. The GLUT1 inhibitor WZB117 reversed the decreases in glucose content in the medium, the increases in glucose uptake, the increases in the expression and membrane transport ratio of GLUT1 caused by AT1-AA. The N-glycosyltransferase inhibitor NGI as well as si-STT3A reversed the AT1-AA-induced upregulation of the STT3A-GLUT1-glucose uptake effect. This study demonstrates that AT1-AA lowers the blood glucose level of fetuses via the STT3A-GLUT1-glucose uptake axis in liver.