ArticleDiabetes2014
Combined therapy with GABA and proinsulin/alum acts synergistically to restore long-term normoglycemia by modulating T-cell autoimmunity and promoting β-cell replication in newly diabetic NOD mice.
Article in Diabetes, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 48 citations in OpenAlex.
- Exploring the Physiological Effects and Mechanisms of Gamma-Aminobutyric Acid in Food Systems.Foods (Basel, Switzerland) · 2026Review
- Combatting psoriasis with nanomedicine: gamma-amino butyric acid-chitosan nanoparticles as a targeted anti-psoriatic therapy.Inflammopharmacology · 2026Article
- Fecal microbiome and metabolome dynamics during immunotherapy-based total neoadjuvant therapy in rectal cancer: associations with treatment response and toxicity.Frontiers in immunology · 2026Article
- The renoprotective activity of amikacin-gamma-amino butyric acid-chitosan nanoparticles: a comparative study.Inflammopharmacology · 2024Article
- The role of GABA in type 1 diabetes.Frontiers in endocrinology · 2024Review
- GABA and Combined GABA with GAD65-Alum Treatment Alters Th1 Cytokine Responses of PBMCs from Children with Recent-Onset Type 1 Diabetes.Biomedicines · 2023Article
- The GABA and GABA-Receptor System in Inflammation, Anti-Tumor Immune Responses, and COVID-19.Biomedicines · 2023Review
- Effects of acute intravenous lipopolysaccharide administration on the plasma lipidome and metabolome in lactating Holstein cows experiencing hyperlipidemia.Metabolomics : Official journal of the Metabolomic Society · 2022Article
- Article
- GABA Administration Ameliorates Sjogren's Syndrome in Two Different Mouse Models.Biomedicines · 2022Article
- Recent advances of γ-aminobutyric acid: Physiological and immunity function, enrichment, and metabolic pathway.Frontiers in nutrition · 2022Review
- A GABA-receptor agonist reduces pneumonitis severity, viral load, and death rate in SARS-CoV-2-infected mice.Frontiers in immunology · 2022Article
- B cell-derived GABA elicits IL-10Nature · 2021Article
- Effects of sustained GABA releasing implants on pancreatic islets in mice.Drug delivery and translational research · 2021Article
- GABAergic signaling by cells of the immune system: more the rule than the exception.Cellular and molecular life sciences : CMLS · 2021Review
- GABAViruses · 2021Article
- Homotaurine limits the spreading of T cell autoreactivity within the CNS and ameliorates disease in a model of multiple sclerosis.Scientific reports · 2021Article
- GABABiomedicines · 2021Article
- GABA administration prevents severe illness and death following coronavirus infection in mice.bioRxiv : the preprint server for biology · 2020Article
- Single-cell RNA-seq with spike-in cells enables accurate quantification of cell-specific drug effects in pancreatic islets.Genome biology · 2020Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Antigen-based therapies (ABTs) fail to restore normoglycemia in newly diabetic NOD mice, perhaps because too few β-cells remain by the time that ABT-induced regulatory responses arise and spread. We hypothesized that combining a fast-acting anti-inflammatory agent with an ABT could limit pathogenic responses while ABT-induced regulatory responses arose and spread. γ-Aminobutyric acid (GABA) administration can inhibit inflammation, enhance regulatory T-cell (Treg) responses, and promote β-cell replication in mice. We examined the effect of combining a prototypic ABT, proinsulin/alum, with GABA treatment in newly diabetic NOD mice. Proinsulin/alum monotherapy failed to correct hyperglycemia, while GABA monotherapy restored normoglycemia for a short period. Combined treatment restored normoglycemia in the long term with apparent permanent remission in some mice. Proinsulin/alum monotherapy induced interleukin (IL)-4- and IL-10-secreting T-cell responses that spread to other β-cell autoantigens. GABA monotherapy induced moderate IL-10 (but not IL-4) responses to β-cell autoantigens. Combined treatment synergistically reduced spontaneous type 1 T-helper cell responses to autoantigens, ABT-induced IL-4 and humoral responses, and insulitis, but enhanced IL-10 and Treg responses and promoted β-cell replication in the islets. Thus, combining ABT with GABA can inhibit pathogenic T-cell responses, induce Treg responses, promote β-cell replication, and effectively restore normoglycemia in newly diabetic NOD mice. Since these treatments appear safe for humans, they hold promise for type 1 diabetes intervention.
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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.