Exendin-9,39(Mayo Clinic)(Exendin-9,39(Mayo Clinic)) - 药物靶点：GLP-1R_在研适应症：2型糖尿病_专利_临床

概要

基本信息

药物类型

合成多肽

别名-

靶点

GLP-1R

作用机制

GLP-1R拮抗剂(胰高血糖素样肽-1拮抗剂)

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

National Institute of Diabetes & Digestive & Kidney Diseases

非在研机构

Mayo Clinic

最高研发阶段临床3期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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关联

8

项与 Exendin-9,39(Mayo Clinic) 相关的临床试验

NCT04466566 / Recruiting临床3期IIT

Effect of Genetic Variation in the GLP-1 Receptor on Beta-cell Function During Fasting and Hyperglycemia in Nondiabetic Humans

The GLP-1 receptor (GLP1R) gene is found on the beta cells of the pancreas. Its role is in the control of blood sugar level by enhancing insulin secretion from the pancreas after eating a meal. The purpose of this research study to find out how genetic variations in GLP1R alter insulin secretion, in the fasting state and when blood sugars levels are elevated.

开始日期2022-10-17

申办/合作机构

Mayo Clinic

[+1]

NCT04466618 / Completed临床3期IIT

To Determine the Effect of Endogenous GLP-1 Secretion on Islet Function in People With and Without Type 2 Diabetes

GLP-1 is a hormone made by the body that promotes the production of insulin in response to GLP-1 is produced within the islets expressing prohormone convertase 1/3eating. However, there is increasing evidence that this hormone might help support the body's ability to produce insulin when diabetes develops. The purpose of this study is to determine the effect of endogenous GLP-1 secretion on insulin secretion in people with and without type 2 diabetes.

开始日期2021-04-15

申办/合作机构

Mayo Clinic

[+1]

NCT04459338 / Completed临床3期IIT

A Dose-response Study Examining the Contribution of GLP-1 Receptor Signaling to Glucagon-stimulated Insulin Secretion

The GLP-1 receptor (GLP1R) gene is found on the beta cells of the pancreas. Its role is in the control of blood sugar level by enhancing insulin secretion from the pancreas after eating a meal. The purpose of this research study is to evaluate the role of GLP1R in the response to elevated glucagon concentrations.

开始日期2021-03-04

申办/合作机构

Mayo Clinic

[+1]

100 项与 Exendin-9,39(Mayo Clinic) 相关的临床结果

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100 项与 Exendin-9,39(Mayo Clinic) 相关的转化医学

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100 项与 Exendin-9,39(Mayo Clinic) 相关的专利（医药）

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17

项与 Exendin-9,39(Mayo Clinic) 相关的文献（医药）

2025-01-01·Experimental Neurology

Lactiplantibacillus plantarum SG5 inhibits neuroinflammation in MPTP-induced PD mice through GLP-1/PGC-1α pathway

Article

作者: Chen, Jinhu ; Ma, Xin ; Wang, Yanqin ; Xie, Siyou ; Qi, Yueyan ; Yu, Xueping ; Dong, Yuxuan ; Yu, Yang

Mounting evidence suggests that alterations in gut microbial composition play an active role in the pathogenesis of Parkinson's disease (PD). Probiotics are believed to modulate gut microbiota, potentially influencing PD development through the microbiota-gut-brain axis. However, the potential beneficial effects of Lactiplantibacillus plantarum SG5 (formerly known as Lactobacillus plantarum, abbreviated as L. plantarum) on PD and its underlying mechanisms remain unclear. In this study, we employed immunofluorescence, Western blotting, ELISA, and 16S rRNA gene sequencing to investigate the neuroprotective effects of L. plantarum SG5 against neuroinflammation in an MPTP-induced PD model and to explore the underlying mechanisms. Our results demonstrated that L. plantarum SG5 ameliorated MPTP-induced motor deficits, dopaminergic neuron loss, and elevated α-synuclein protein levels. Furthermore, SG5 inhibited MPTP-triggered overactivation of microglia and astrocytes in the substantia nigra (SN), attenuated disruption of both blood-brain and intestinal barriers, and suppressed the release of inflammatory factors in the colon and SN. Notably, SG5 modulated the composition and structure of the gut microbiota in mice. The MPTP-induced decrease in colonic GLP-1 secretion was reversed by SG5 treatment, accompanied by increased expression of GLP-1R and PGC-1α in the SN. Importantly, the GLP-1R antagonist Exendin 9-39 and PGC-1α inhibitor SR18292 attenuated the protective effects of SG5 in PD mice. In conclusion, we demonstrate a neuroprotective role of L. plantarum SG5 in the MPTP-induced PD mouse model, which likely involves modulation of the gut microbiota and, significantly, the GLP-1/PGC-1α signaling pathway.

2024-05-22·The Journal of Neuroscience

GLP-1 in the Hypothalamic Paraventricular Nucleus Promotes Sympathetic Activation and Hypertension

Article

作者: Xu, Xiao-Yu ; Zhu, Guo-Qing ; Chen, Ai-Dong ; Li, Yue-Hua ; Wang, Yi-Ming ; Chen, Jun-Liu ; Wang, Jing-Xiao ; Dai, Min ; Chen, Qi

Glucagon-like peptide-1 (GLP-1) and its analogs are widely used for diabetes treatment. The paraventricular nucleus (PVN) is crucial for regulating cardiovascular activity. This study aims to determine the roles of GLP-1 and its receptors (GLP-1R) in the PVN in regulating sympathetic outflow and blood pressure. Experiments were carried out in male normotensive rats and spontaneously hypertensive rats (SHR). Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded. GLP-1 and GLP-1R expressions were present in the PVN. PVN microinjection of GLP-1R agonist recombinant human GLP-1 (rhGLP-1) or EX-4 increased RSNA and MAP, which were prevented by GLP-1R antagonist exendin 9-39 (EX9-39) or GLP-1R antagonist 1, superoxide scavenger tempol, antioxidant N-acetylcysteine, NADPH oxidase (NOX) inhibitor apocynin, adenylyl cyclase (AC) inhibitor SQ22536 or protein kinase A (PKA) inhibitor H89. PVN microinjection of rhGLP-1 increased superoxide production, NADPH oxidase activity, cAMP level, AC, and PKA activity, which were prevented by SQ22536 or H89. GLP-1 and GLP-1R were upregulated in the PVN of SHR. PVN microinjection of GLP-1 agonist increased RSNA and MAP in both WKY and SHR, but GLP-1 antagonists caused greater effects in reducing RSNA and MAP in SHR than in WKY. The increased superoxide production and NADPH oxidase activity in the PVN of SHR were augmented by GLP-1R agonists but attenuated by GLP-1R antagonists. These results indicate that activation of GLP-1R in the PVN increased sympathetic outflow and blood pressure via cAMP-PKA–mediated NADPH oxidase activation and subsequent superoxide production. GLP-1 and GLP-1R upregulation in the PVN partially contributes to sympathetic overactivity and hypertension.

2023-12-31·Redox Report

Liraglutide ameliorates oxidized LDL-induced endothelial dysfunction by GLP-1R-dependent downregulation of LOX-1-mediated oxidative stress and inflammation

Article

作者: Kaizu, Xu ; Ying, Wu ; Meiyan, Song ; Liming, Lin ; Meifang, Wu ; Wen, Chen

OBJECTIVETo investigate the effects of glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide on endothelial dysfunction in LDL receptor-deficient (LDLR-KO) mice and ox-LDL-challenged human umbilical vein endothelial cells (HUVECs) and its possible mechanism.METHODSLDLR-KO mice were randomly treated with normal saline, liraglutide, or liraglutide plus a GLP-1R antagonist exendin-9 for four weeks. In parallel, HUVECs were cultured with ox-LDL alone or combined with liraglutide, in the presence or absence of lectin-like ox-LDL receptor-1(LOX-1) overexpression or GLP-1R knockdown. Endothelial-dependent relaxation and LOX-1 protein expression of thoracic aorta, circulating levels of oxidative and inflammatory markers in mice, and cell survival, reactive oxygen species production, and expression of adhesion molecules and signal regulators in ox-LDL cultured endothelial cells were measured.RESULTSliraglutide effectively enhanced acetylcholine-induced vasodilation, reduced LOX-1 expression in aortas, and decreased circulatory oxidative and inflammatory levels in LDLR-KO mice, which were abolished by cotreatment with exendin-9. HUVECs exposed to ox-LDL exhibited reduced cell viability, increased reactive oxygen species production and apoptosis, and elevated protein expression of ICAM-1, VCAM-1, LOX-1, NOX4, and NF-κB, which were markedly ameliorated by liraglutide treatment. The protective effects of liraglutide against ox-LDL-induced cell injury were abrogated in HUVECs overexpressing LOX-1 or silencing GLP-1R.CONCLUSIONSLiraglutide improved oxidized LDL-induced endothelial dysfunction via GLP-1R-dependent downregulation of LOX-1-mediated oxidative stress and inflammation.

100 项与 Exendin-9,39(Mayo Clinic) 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
2型糖尿病	临床3期	美国	National Institute of Diabetes & Digestive & Kidney Diseases	2021-04-15
糖尿病	临床前	美国	Mayo Clinic	2014-05-01
胃肠道疾病	临床前	美国	National Institute of Diabetes & Digestive & Kidney Diseases	2014-05-01
胃肠道疾病	临床前	美国	Mayo Clinic	2014-05-01
肥胖	临床前	美国	National Institute of Diabetes & Digestive & Kidney Diseases	2014-05-01
肥胖	临床前	美国	Mayo Clinic	2014-05-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02762708 (Microbiome, CTgov)	临床2期	2型糖尿病 \| 肥胖	12	Roux-en-Y Gastric Bypass (RYGB) (Roux-en-Y Gastric Bypass (RYGB))	選觸壓蓋積範鏇構簾齋(網構醖餘獵顧鑰壓觸醖) = 築壓齋願觸觸蓋餘構襯淵窪遞襯窪醖遞積廠夢 (構蓋齋糧簾蓋構獵窪壓, 鏇蓋襯艱淵艱顧簾夢壓 ~ 網蓋鬱鏇壓鹽齋獵醖鹹) 更多	-	2022-05-03
				Caloric Restriction (Caloric Restriction)	選觸壓蓋積範鏇構簾齋(網構醖餘獵顧鑰壓觸醖) = 願艱鏇鹽艱範構醖築膚淵窪遞襯窪醖遞積廠夢 (構蓋齋糧簾蓋構獵窪壓, 簾鹹鏇製築製鹹醖壓糧 ~ 鬱壓糧糧遞膚蓋醖夢窪) 更多
NCT02779075 (CTgov)	N/A	肥胖	29	Saline (Saline)	壓製糧衊衊製憲積鏇窪(衊淵範壓蓋觸膚築夢襯) = 憲網選範醖夢範鹹鹽鏇築鬱壓衊齋鬱選製窪艱 (壓範觸遞憲構鹽構蓋網, 廠鏇淵餘壓網鹹廠鏇齋 ~ 觸齋齋築築窪鹽憲築夢) 更多	-	2020-05-01
				Exendin-9,39 (Exendin-9,39)	壓製糧衊衊製憲積鏇窪(衊淵範壓蓋觸膚築夢襯) = 衊鏇範齋壓鹽顧鬱觸襯築鬱壓衊齋鬱選製窪艱 (壓範觸遞憲構鹽構蓋網, 積餘鬱獵醖艱觸齋壓簾 ~ 窪願網鏇廠獵願鹹鏇繭) 更多