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胰岛星状细胞通过Wnt5a调节Min6细胞中的胰岛素分泌。

Islet Stellate Cells Regulate Insulin Secretion via Wnt5a in Min6 Cells.

作者信息

Xu Wei, Jones Peter M, Geng Houfa, Li Rui, Liu Xuekui, Li Yinxia, Lv Qian, Liu Ying, Wang Jie, Wang Xiuli, Sun Zilin, Liang Jun

机构信息

Department of Endocrinology, Xuzhou Central Hospital, Xuzhou Institute of Medical Sciences, Xuzhou Clinical School of Nanjing Medical University, Affiliated Hospital of Medical School of Southeast University, Xuzhou, Jiangsu, China.

Diabetes Research Group, Division of Diabetes & Nutritional Sciences, School of Medicine, King's College London, London, UK.

出版信息

Int J Endocrinol. 2020 Feb 24;2020:4708132. doi: 10.1155/2020/4708132. eCollection 2020.

Abstract

BACKGROUND

Type 2 diabetes mellitus is a serious public health problem worldwide. Accumulating evidence has shown that -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 -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.

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 -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.

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 Ca 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 -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.

CONCLUSION

ISCs regulate insulin secretion from Min6 cells through the Wnt5a protein-induced Wnt-calcium and FoxO1-PDX1-GLUT2-insulin signalling cascades.

摘要

背景

2型糖尿病是全球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的重要潜在机制。胰岛星状细胞(ISCs)生理状态的变化及其对β细胞功能障碍的影响是糖尿病的重要潜在机制。胰岛星状细胞(ISCs)生理状态的变化及其对……的影响。

方法

在用ISC上清液或外源性Wnt5a培养后,通过估计对高糖刺激的胰岛素水平来检测Min6细胞的葡萄糖刺激胰岛素分泌(GSIS)。蛋白质免疫印迹法和定量实时聚合酶链反应(qRT-PCR)分析用于观察β细胞功能障碍的变化,β细胞功能障碍是糖尿病的重要潜在机制。胰岛星状细胞(ISCs)生理状态的变化及其对……的影响。

结果

我们观察到,与用db/db小鼠ISC上清液共培养 的Min6细胞相比,用db/m小鼠ISC上清液体外共培养的Min6细胞胰岛素分泌显著增加;与对照Min6细胞相比,用db/m小鼠ISC上清液和外源性Wnt—5a体外培养的Min6细胞内钙浓度增加。与单独培养的Min6细胞相比,用外源性Wnt5a培养Min6细胞导致pCamKII、pFoxO1、PDX-1和Glut2水平显著增加;这种处理进一步降低了Ror2和Cask表达,但不影响β细胞功能障碍是糖尿病的重要潜在机制。胰岛星状细胞(ISCs)生理状态的变化及其对……的影响。

结论

ISCs通过Wnt5a蛋白诱导的Wnt-钙和FoxO1-PDX1-GLUT-胰岛素信号级联反应调节Min6细胞的胰岛素分泌。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f64e/7060442/70b9a0756aef/IJE2020-4708132.001.jpg

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