NMDA Receptor Antagonists Increase the Release of GLP-1 From Gut Endocrine Cells.
NMDA Receptor Antagonists Increase the Release of GLP-1 From Gut Endocrine Cells.
复制标题
DOI：
10.3389/fphar.2022.861311
复制
发表时间：
2022
影响因子：
5.6
通讯作者：
de Wet, Heidi
中科院分区：
文献类型：
--
作者：
Cyranka, Malgorzata;Monfeuga, Thomas;Vedovato, Natascia;Larabee, Chelsea M.;Chandran, Anandhakumar;Toledo, Enrique M.;de Wet, Heidi
关键词：
2型糖尿病(T2 DM)仍然是现代社会面临的最紧迫的健康问题之一。几种抗糖尿病药物目前正在临床上用于治疗高血糖，但需要有效恢复患者胰岛功能的新疗法。最近的研究表明，N-甲基-D-天冬氨酸受体拮抗剂对小鼠和人胰岛细胞的胰岛素释放和β细胞活性均有促进作用。此外，在一项小型临床试验中，糖尿病患者口服非处方药NMDA受体拮抗剂右美沙芬可改善糖耐量，增加胰岛素释放。然而，NMDA受体拮抗剂对胰岛素激素GLP-1分泌的影响尚未得到测试，也不知道NMDA受体拮抗剂如何改变胃肠激素的分泌。本研究首次证明，与β-细胞相似，NMDA型受体拮抗剂MK-801可促进小鼠L肠内分泌模型细胞株GLU-Tag细胞释放GLP-1。此外，我们报道了GLUTag细胞的3‘mRNA表达谱，特别是谷氨酸激活的受体。我们的结论是，如果要寻求NMDA受体拮抗剂作为T2 DM口服治疗的替代药物，那么充分研究这些药物对胃肠激素释放的影响是至关重要的，特别是对胰岛素激素的影响。
Type 2 diabetes mellitus (T2DM) remains one of the most pressing health issues facing modern society. Several antidiabetic drugs are currently in clinical use to treat hyperglycaemia, but there is a need for new treatments that effectively restore pancreatic islet function in patients. Recent studies reported that both murine and human pancreatic islets exhibit enhanced insulin release and β-cell viability in response to N-methyl-D-aspartate (NMDA) receptor antagonists. Furthermore, oral administration of dextromethorphan, an over-the-counter NMDA receptor antagonist, to diabetic patients in a small clinical trial showed improved glucose tolerance and increased insulin release. However, the effects of NMDA receptor antagonists on the secretion of the incretin hormone GLP-1 was not tested, and nothing is known regarding how NMDA receptor antagonists may alter the secretion of gut hormones. This study demonstrates for the first time that, similar to β-cells, the NMDA receptor antagonist MK-801 increases the release of GLP-1 from a murine L-cell enteroendocrine model cell line, GLUTag cells. Furthermore, we report the 3′ mRNA expression profiling of GLUTag cells, with a specific focus on glutamate-activated receptors. We conclude that if NMDA receptor antagonists are to be pursued as an alternative, orally administered treatment for T2DM, it is essential that the effects of these drugs on the release of gut hormones, and specifically the incretin hormones, are fully investigated.
登录
查看更多内容
影响因子：
14.9
作者：
Howe KL;Achuthan P;Allen J;Allen J;Alvarez-Jarreta J;Amode MR;Armean IM;Azov AG;Bennett R;Bhai J;Billis K;Boddu S;Charkhchi M;Cummins C;Da Rin Fioretto L;Davidson C;Dodiya K;El Houdaigui B;Fatima R;Gall A;Garcia Giron C;Grego T;Guijarro-Clarke C;Haggerty L;Hemrom A;Hourlier T;Izuogu OG;Juettemann T;Kaikala V;Kay M;Lavidas I;Le T;Lemos D;Gonzalez Martinez J;Marugán JC;Maurel T;McMahon AC;Mohanan S;Moore B;Muffato M;Oheh DN;Paraschas D;Parker A;Parton A;Prosovetskaia I;Sakthivel MP;Salam AIA;Schmitt BM;Schuilenburg H;Sheppard D;Steed E;Szpak M;Szuba M;Taylor K;Thormann A;Threadgold G;Walts B;Winterbottom A;Chakiachvili M;Chaubal A;De Silva N;Flint B;Frankish A;Hunt SE;IIsley GR;Langridge N;Loveland JE;Martin FJ;Mudge JM;Morales J;Perry E;Ruffier M;Tate J;Thybert D;Trevanion SJ;Cunningham F;Yates AD;Zerbino DR;Flicek P
通讯作者：
Flicek P
影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
影响因子：
6.9
作者：
Cyranka, Malgorzata;Veprik, Anna;de Wet, Heidi
通讯作者：
de Wet, Heidi
影响因子：
7.7
作者：
Roberts, Geoffrey P.;Larraufie, Pierre;Gribble, Fiona M.
通讯作者：
Gribble, Fiona M.
DOI：
10.1126/science.aat5236
发表时间：
2018-09-21
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kaelberer MM;Buchanan KL;Klein ME;Barth BB;Montoya MM;Shen X;Bohórquez DV
通讯作者：
Bohórquez DV