An excessive increase in glutamate contributes to glucose-toxicity in β-cells via activation of pancreatic NMDA receptors in rodent diabetes
点击次数：
影响因子：
3.998
DOI码：
10.1038/srep44120
所属单位：
中南大学
发表刊物：
Scientific Reports
刊物所在地：
加拿大
摘要：
In the nervous system, excessive activation of NMDA receptors causes neuronal injury. Although activation of NMDARs has been proposed to contribute to the progress of diabetes, little is known about the effect of excessive long-term activation of NMDARs on β-cells, especially under the challenge of hyperglycemia. Here we thoroughly investigated whether endogenous glutamate aggravated β-cell dysfunction under chronic exposure to high-glucose via activation of NMDARs. The glutamate level was increased in plasma of diabetic mice or patients and in the supernatant of β-cell lines after treatment with high-glucose for 72 h. Decomposing the released glutamate improved GSIS of β-cells under chronic high-glucose exposure. Long-term treatment of β-cells with NMDA inhibited cell viability and decreased GSIS. These effects were eliminated by GluN1 knockout. The NMDAR antagonist MK-801 or GluN1 knockout prevented high-glucose-induced dysfunction in β-cells. MK-801 also decreased the expression of pro-inflammatory cytokines, and inhibited I-κB degradation, ROS generation and NLRP3 inflammasome expression in β-cells exposed to high-glucose. Furthermore, another NMDAR antagonist, Memantine, improved β-cells function in diabetic mice. Taken together, these findings indicate that an increase of glutamate may contribute to the development of diabetes through excessive activation of NMDARs in β-cells, accelerating β-cells dysfunction and apoptosis induced by hyperglycemia.
备注：
Q1
合写作者：
Chen Li, Xiangping Peng, Jia Guo, Shaojie Yue, Wei Liu, Feiyan Zhao, Jianzhong Han, Yanhong Huang, Yang Li, Qingmei Cheng, Zhiguang Zhou, Chen Chen, Ziqiang Luo
第一作者：
Xiaoting Huang
论文类型：
期刊论文
通讯作者：
Dandan Feng
学科门类：
护理学
文献类型：
J
卷号：
7
页面范围：
44120
是否译文：
否
收录刊物：
SCI
学位：医学博士学位
职称：教授
学科：护理学
所在单位：湘雅护理学院
