Delving into the Latest Updates on Exendin-9,39(Mayo Clinic) with Synapse

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.

Start Date17 Oct 2022

Sponsor / Collaborator

Mayo Clinic

[+1]

NCT04466618 / CompletedPhase 3IIT

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.

Start Date15 Apr 2021

Sponsor / Collaborator

Mayo Clinic

[+1]

NCT04459338 / CompletedPhase 3IIT

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.

Start Date04 Mar 2021

Sponsor / Collaborator

Mayo Clinic

[+1]

100 Clinical Results associated with Exendin-9,39(Mayo Clinic)

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100 Translational Medicine associated with Exendin-9,39(Mayo Clinic)

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100 Patents (Medical) associated with Exendin-9,39(Mayo Clinic)

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17

Literatures (Medical) associated with Exendin-9,39(Mayo Clinic)

01 Jan 2025·Experimental Neurology

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

Article

Author: 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.

22 May 2024·The Journal of Neuroscience

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

Article

Author: 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.

31 Dec 2023·Redox Report

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

Article

Author: 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 Deals associated with Exendin-9,39(Mayo Clinic)

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R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Diabetes Mellitus, Type 2	Phase 3	US	National Institute of Diabetes & Digestive & Kidney Diseases	15 Apr 2021
Diabetes Mellitus	Preclinical	US	Mayo Clinic	01 May 2014
Gastrointestinal Diseases	Preclinical	US	National Institute of Diabetes & Digestive & Kidney Diseases	01 May 2014
Gastrointestinal Diseases	Preclinical	US	Mayo Clinic	01 May 2014
Obesity	Preclinical	US	National Institute of Diabetes & Digestive & Kidney Diseases	01 May 2014
Obesity	Preclinical	US	Mayo Clinic	01 May 2014

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02762708 (Microbiome, CTgov)	Phase 2	Diabetes Mellitus, Type 2 \| Obesity	12	Roux-en-Y Gastric Bypass (RYGB) (Roux-en-Y Gastric Bypass (RYGB))	enbxemsizh(azhmgkjvqx) = pwnocltglb yjstmhyjvn (broyevcvdw, heigqbvybx - ihmrnzzagt) View more	-	03 May 2022
				Caloric Restriction (Caloric Restriction)	enbxemsizh(azhmgkjvqx) = qdvnecizwg yjstmhyjvn (broyevcvdw, sxlawoytfh - petwbkskvu) View more
NCT02779075 (CTgov)	Not Applicable	Obesity	29	Saline (Saline)	wuxvntewxt(ktbaispmuu) = nftnhwlwct bttccsacch (ddtmgqtsuh, bhcgxtdtbq - ymxbbaqwtk) View more	-	01 May 2020
				Exendin-9,39 (Exendin-9,39)	wuxvntewxt(ktbaispmuu) = wedjlychil bttccsacch (ddtmgqtsuh, tmhkegptsn - odwncbowsz) View more