ArticleDiabetologia2022
GLP-1 receptor nitration contributes to loss of brain pericyte function in a mouse model of diabetes.
Article in Diabetologia, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Effect of antidiabetic drugs in Alzheimer´s disease: a systematic review of preclinical and clinical studies.Molecular neurodegeneration · 2025Pooled it
- Diabetic cerebral microvascular disorder: from key pathologies to targeted interventions.Annals of medicine · 2026Review
- The Liver-brain Axis: A Three-stage Model Linking MASLD to Cognitive Impairment and Dementia.Journal of molecular neuroscience : MN · 2026Review
- Therapeutic Potential of Curcumin in Diabetic Cardiomyopathy: Modulation of Pyroptosis Pathways.Cardiovascular drugs and therapy · 2026Article
- Systemic effects of type 2 diabetes therapies: an integrated perspective on the cardio-renal- cerebral-metabolic axis.Frontiers in medicine · 2026Review
- Repurposing glucagon-like peptide-1 receptor agonists for the treatment of neurodegenerative disorders.Nature aging · 2026Review
- The stem cell within the vessel wall: multipotent pericytes modulating β-cell function and diabetic complications.Stem cell research & therapy · 2025Review
- Transpupillary in vivo two-photon imaging reveals enhanced surveillance of retinal microglia in diabetic mice.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The Impact of Glucagon-like Peptide-1 Receptor Agonists on Erectile Function: Friend or Foe?Biomolecules · 2025Review
- Effect and mechanism of GLP-1 on cognitive function in diabetes mellitus.Frontiers in neuroscience · 2025Review
- All GLP-1 Agonists Should, Theoretically, Cure Alzheimer's Dementia but Dulaglutide Might Be More Effective Than the Others.Journal of clinical medicine · 2024Review
- Special Issue "Pathophysiology and Treatment of Alzheimer's Disease".International journal of molecular sciences · 2024Article
- Deciphering the connection: Diabetes, pericyte dysfunction, and their impact on cardiovascular health.Journal of diabetes · 2024Article
- Exploring the association between weight loss-inducing medications and multiple sclerosis: insights from the FDA adverse event reporting system database.Therapeutic advances in neurological disorders · 2024Article
- Timing matters in the use of renin-angiotensin system modulators and COVID-related cognitive and cerebrovascular dysfunction.PloS one · 2024Article
- Emerging Links between Cerebral Blood Flow Regulation and Cognitive Decline: A Role for Brain Microvascular Pericytes.Aging and disease · 2023Review
- Glucagon-like peptide-1 (GLP-1) receptor agonists and neuroinflammation: Implications for neurodegenerative disease treatment.Pharmacological research · 2022Review
- Accelerated amyloid angiopathy and related vascular alterations in a mixed murine model of Alzheimer´s disease and type two diabetes.Fluids and barriers of the CNS · 2022Article
- Calpain Inhibitor Calpeptin Improves Alzheimer's Disease-Like Cognitive Impairments and Pathologies in a Diabetes Mellitus Rat Model.Neurotoxicity research · 2022Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
aims/hypothesisWe have previously shown that diabetes causes pericyte dysfunction, leading to loss of vascular integrity and vascular cognitive impairment and dementia (VCID). Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RAs), used in managing type 2 diabetes mellitus, improve the cognitive function of diabetic individuals beyond glycaemic control, yet the mechanism is not fully understood. In the present study, we hypothesise that GLP-1 RAs improve VCID by preventing diabetes-induced pericyte dysfunction.
methodsMice with streptozotocin-induced diabetes and non-diabetic control mice received either saline (NaCl 154 mmol/l) or exendin-4, a GLP-1 RA, through an osmotic pump over 28 days. Vascular integrity was assessed by measuring cerebrovascular neovascularisation indices (vascular density, tortuosity and branching density). Cognitive function was evaluated with Barnes maze and Morris water maze. Human brain microvascular pericytes (HBMPCs), were grown in high glucose (25 mmol/l) and sodium palmitate (200 μmol/l) to mimic diabetic conditions. HBMPCs were treated with/without exendin-4 and assessed for nitrative and oxidative stress, and angiogenic and blood-brain barrier functions.
resultsDiabetic mice treated with exendin-4 showed a significant reduction in all cerebral pathological neovascularisation indices and an improved blood-brain barrier (p<0.05). The vascular protective effects were accompanied by significant improvement in the learning and memory functions of diabetic mice compared with control mice (p<0.05). Our results showed that HBMPCs expressed the GLP-1 receptor. Diabetes increased GLP-1 receptor expression and receptor nitration in HBMPCs. Stimulation of HBMPCs with exendin-4 under diabetic conditions decreased diabetes-induced vascular inflammation and oxidative stress, and restored pericyte function (p<0.05). CONCLUSIONS/
interpretationThis study provides novel evidence that brain pericytes express the GLP-1 receptor, which is nitrated under diabetic conditions. GLP-1 receptor activation improves brain pericyte function resulting in restoration of vascular integrity and BBB functions in diabetes. Furthermore, the GLP-1 RA exendin-4 alleviates diabetes-induced cognitive impairment in mice. Restoration of pericyte function in diabetes represents a novel therapeutic target for diabetes-induced cerebrovascular microangiopathy and VCID.
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