Impact Factor:3.998
DOI number:10.1038/srep44120
Affiliation of Author(s):中南大学
Journal:Scientific Reports
Place of Publication:加拿大
Abstract: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.
Note:Q1
Co-author: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
First Author:Xiaoting Huang
Indexed by:Journal paper
Correspondence Author:Dandan Feng
Discipline:护理学
Document Type:J
Volume:7
Page Number:44120
Translation or Not:no
Included Journals:SCI