ArticlePloS one2016
An Orally Active Allosteric GLP-1 Receptor Agonist Is Neuroprotective in Cellular and Rodent Models of Stroke.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 46 citations in OpenAlex.
- GLP-1 Receptor Agonist Use Is Associated With Lower Risk of Intracranial Aneurysm Rupture and Rupture Severity.Stroke · 2026Article
- GLP-1 receptor agonists as multisystem therapies: from glycemic control to cardiorenal, neuroimmune, and metabolic disease.Diabetology & metabolic syndrome · 2026Review
- Exendin-4 as a multi-target therapy for Fetal Inflammatory Response Syndrome-induced brain injury.Frontiers in neurology · 2026Review
- GLP-1 Receptor Agonists in Acute Ischemic Stroke and Secondary Stroke Prevention: A Narrative Review of Preclinical and Clinical Evidence.Journal of central nervous system disease · 2026Review
- Article
- Review
- Glucagon-like peptide-1 receptor: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2024 · on this mapReview
- GLP-1 Receptor Agonists: Beyond Diabetes-What the Neurosurgeon Needs to Know.Neurosurgery practice · 2024Review
- From diabetes to diverse domains: the multifaceted roles of GLP-1 receptor agonists.Molecular biology reports · 2024Review
- Diabetes drugs activate neuroprotective pathways in models of neonatal hypoxic-ischemic encephalopathy.EMBO molecular medicine · 2024Article
- Astrocyte KDM4A mediates chemokines and drives neutrophil infiltration to aggravate cerebral ischemia and reperfusion injury.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- Neprilysin inhibitors and risk of Alzheimer's disease: A future perspective.Journal of cellular and molecular medicine · 2024Review
- Association of glucose-lowering drugs with incident stroke and transient ischaemic attacks in primary care patients with type 2 diabetes: disease analyzer database.Acta diabetologica · 2022Article
- Signaling Mechanism for Modulation by GLP-1 and Exendin-4 of GABA Receptors on Rat Retinal Ganglion Cells.Neuroscience bulletin · 2022Article
- Non-peptide agonists and positive allosteric modulators of glucagon-like peptide-1 receptors: Alternative approaches for treatment of Type 2 diabetes.British journal of pharmacology · 2022Review
- Neuroprotective Mechanisms of Glucagon-Like Peptide-1-Based Therapies in Ischemic Stroke: An Update Based on Preclinical Research.Frontiers in neurology · 2022Review
- A quinoxaline-based compound ameliorates bone loss in ovariectomized mice.Experimental biology and medicine (Maywood, N.J.) · 2021Article
- Involvement of non‑coding RNAs in the pathogenesis of myocardial ischemia/reperfusion injury (Review).International journal of molecular medicine · 2021Review
- Glucagon-like peptide-1 receptor agonists as neuroprotective agents for ischemic stroke: a systematic scoping review.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- Brain uptake pharmacokinetics of incretin receptor agonists showing promise as Alzheimer's and Parkinson's disease therapeutics.Biochemical pharmacology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diabetes is a major risk factor for the development of stroke. Glucagon-like peptide-1 receptor (GLP-1R) agonists have been in clinical use for the treatment of diabetes and also been reported to be neuroprotective in ischemic stroke. The quinoxaline 6,7-dichloro-2-methylsulfonyl-3-N-tert- butylaminoquinoxaline (DMB) is an agonist and allosteric modulator of the GLP-1R with the potential to increase the affinity of GLP-1 for its receptor. The aim of this study was to evaluate the neuroprotective effects of DMB on transient focal cerebral ischemia. In cultured cortical neurons, DMB activated the GLP-1R, leading to increased intracellular cAMP levels with an EC50 value about 100 fold that of exendin-4. Pretreatment of neurons with DMB protected against necrotic and apoptotic cell death was induced by oxygen-glucose deprivation (OGD). The neuroprotective effects of DMB were blocked by GLP-1R knockdown with shRNA but not by GLP-1R antagonism. In C57BL/6 mice, DMB was orally administered 30 min prior to middle cerebral artery occlusion (MCAO) surgery. DMB markedly reduced the cerebral infarct size and neurological deficits caused by MCAO and reperfusion. The neuroprotective effects were mediated by activation of the GLP-1R through the cAMP-PKA-CREB signaling pathway. DMB exhibited anti-apoptotic effects by modulating Bcl-2 family members. These results provide evidence that DMB, a small molecular GLP-1R agonist, attenuates transient focal cerebral ischemia injury and inhibits neuronal apoptosis induced by MCAO. Taken together, these data suggest that DMB is a potential neuroprotective agent against cerebral ischemia.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.