Islet Stellate Cells Regulate Insulin Secretion via Wnt5a in Min6 Cells
Islet Stellate Cells Regulate Insulin Secretion via Wnt5a in Min6 Cells
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Min6 细胞中胰岛星状细胞通过 Wnt5a 调节胰岛素分泌
DOI：
10.1155/2020/4708132
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发表时间：
2020-02
影响因子：
2.8
通讯作者：
Jun Liang
中科院分区：
文献类型：
--
作者：
Wei Xu;Peter M.Jones;Houfa Geng;Rui Li;Xuekui Liu;Yinxia Li;Qian Lv;Ying Liu;Jie Wang;Xiuli Wang;Zilin Sun;Jun Liang
背景：2型糖尿病是世界范围内严重的公共卫生问题。越来越多的证据表明，β细胞功能障碍是糖尿病发病的重要机制之一。胰岛星状细胞(ISCs)生理状态的改变及其对β细胞功能的影响在糖尿病的发生发展中起着重要作用。本研究旨在阐明胰岛素样干细胞通过Wnt5a蛋白调节Min6细胞胰岛素分泌的机制。方法：用ISC上清液或外源Wnt5a培养Min6细胞，通过测定高糖刺激下的胰岛素水平来检测葡萄糖刺激的胰岛素分泌(GSIS)。用Western blotting和实时定量聚合酶链式反应(QRT-PCR)分析WNT和胰岛素分泌途径中β-连环蛋白、受体酪氨酸激酶样孤儿受体2(ROR2)、钙(2+)/钙调蛋白依赖的蛋白激酶II(CaMKII)、FoxO1、胰腺和十二指肠同源盒1(PDX1)、葡萄糖转运蛋白2(Glut2)、胰岛素和CaskmRNA和蛋白水平的变化。用流式细胞仪检测细胞内钙离子浓度。结果：与db/m小鼠ISCs上清液共培养的Min6细胞的胰岛素分泌量明显高于与Db/db小鼠ISCs上清液共培养的Min6细胞，加入db/m小鼠ISCs上清液和外源Wnt5a的Min6细胞的细胞内钙离子浓度较对照Min6细胞明显升高。与单独培养的Min6细胞相比，与外源Wnt5a共同培养的Min6细胞pCamKII、pFoxO1、Pdx-1和Glt2的表达显著增加；这种处理进一步降低了Ror2和Cask的表达，但不影响β-catenin的表达。结论：ISCS通过Wnt5a蛋白诱导的WNT-钙和FoxO1-PDX1-GLUT2-胰岛素信号转导通路调节Min6细胞的胰岛素分泌。
ABSTRACT.Background: Type 2 diabetes mellitus is a serious public health problem worldwide. Accumulating evidence has shown that β-cell dysfunction is an important mechanism underlying diabetes mellitus. The changes in the physiological state of islet stellate cells (ISCs) and the effects of these cells on β cell function play an important role in the development of diabetes. This study aimed to elucidate the mechanism by which ISCs regulate insulin secretion from Min6 cells via the Wnt5a protein. Methods: Glucose-stimulated insulin secretion (GSIS) from Min6 cells was examined by estimating the insulin levels in response to high glucose challenge after culture with ISC supernatant or exogenous Wnt5a. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) analyses were used to observe changes in the β-catenin, Receptor Tyrosine Kinase-Like Orphan Receptor 2 (Ror2), Ca (2+)/calmodulin (CaM)-dependent protein kinase II.(CamKII), Fork head Box O1 (FoxO1), pancreatic and duodenal homeobox 1 (PDX1), Glucose transporter 2 (Glut2), Insulin, and Cask mRNA and protein levels in the Wnt and insulin secretory pathways. Flow cytometry was used to confirm the intracellular Ca2+ concentration in Min6 cells. Results: We observed a significant increase in insulin secretion from Min6 cells cocultured in vitro with supernatant from db/m mouse ISCs compared to that from Min6 cells cocultured with supernatant from db/db mouse ISCs; The intracellular Ca2 + concentration in Min6 cells increased in cultured in vitro with supernatant from db/m mouse ISCs and exogenous Wnt5a compared to that from Control Min6 cells. Culture of Min6 cells with exogenous Wnt5a caused a significant increase in pCamKII, pFoxO1, PDX-1, and Glut2 levels compared to those in Min6 cells cultured alone; this treatment further decreased Ror2 and Cask expression but did not affect β-catenin expression. Conclusion: ISCs regulate insulin secretion from Min6 cells through the Wnt5a protein-induced Wnt-calcium and FoxO1-PDX1-GLUT2-insulin signalling cascades..
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影响因子：
3.9
作者：
Da Silva Xavier G
通讯作者：
Da Silva Xavier G
TCF7L2在控制葡萄糖稳态，胰腺形态，血管形成和再生中扮演多效性角色。
影响因子：
4.6
作者：
Facchinello N;Tarifeño-Saldivia E;Grisan E;Schiavone M;Peron M;Mongera A;Ek O;Schmitner N;Meyer D;Peers B;Tiso N;Argenton F
通讯作者：
Argenton F
影响因子：
4.3
作者：
Li FF;Chen BJ;Li W;Li L;Zha M;Zhou S;Bachem MG;Sun ZL
通讯作者：
Sun ZL
影响因子：
8.2
作者：
Hogan MF;Hull RL
通讯作者：
Hull RL
影响因子：
3.7
作者：
Xinger Wu;W. Liang;H. Guan;Juan Liu;Liehua Liu;Hai Li;Xiaoying He;Jing Zheng;Jie Chen
通讯作者：
Xinger Wu;W. Liang;H. Guan;Juan Liu;Liehua Liu;Hai Li;Xiaoying He;Jing Zheng;Jie Chen