ArticleDiabetologia2017
Paracrine GABA and insulin regulate pancreatic alpha cell proliferation in a mouse model of type 1 diabetes.
Article in Diabetologia, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 67 citations in OpenAlex.
- A randomized trial of oral gamma aminobutyric acid (GABA) or the combination of GABA with glutamic acid decarboxylase (GAD) on pancreatic islet endocrine function in children with newly diagnosed type 1 diabetes.Nature communications · 2022Trial
- Supplementation of γ-Aminobutyric Acid as a Functional Nutrient.Nutrients · 2026Review
- Fluorine-18 Radiolabeled Single-Chain Antibody Variable Fragment 1F4 Targets α1-Subunit Gamma-Aminobutyric Acid Type A Receptors in Mice.Journal of medicinal chemistry · 2026Article
- Review
- Article
- Targeting GABA signaling in type 1 diabetes and its complications- an update on the state of the art.Pharmacological reports : PR · 2025Review
- PET imaging of GABAEJNMMI research · 2024Article
- Neuronal Nitric Oxide Synthase Regulates Cerebellar Parallel Fiber Slow EPSC in Purkinje Neurons by Modulating STIM1-Gated TRPC3-Containing Channels.Cerebellum (London, England) · 2024Article
- Prophylactic Supplementation with Lactobacillus Reuteri or Its Metabolite GABA Protects Against Acute Ischemic Cardiac Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Plasma γ-Aminobutyric Acid (GABA) Concentrations in Lactating Holstein Cows during Thermoneutral and Heat Stress Conditions and Their Relationships with Circulating Glucose, Insulin and Progesterone Levels.Veterinary sciences · 2024Article
- Lithium and exercise ameliorate insulin-deficient hyperglycemia by independently attenuating pancreatic α-cell mass and hepatic gluconeogenesis.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2024Article
- Retinal and metabolic changes in a high-fat diet (HFD)+STZ model of Type II diabetes.Molecular vision · 2024Article
- The role of GABA in type 1 diabetes.Frontiers in endocrinology · 2024Review
- Paired box 6 gene delivery preserves beta cells and improves islet transplantation efficacy.EMBO molecular medicine · 2023Article
- Hyperglucagonaemia in diabetes: altered amino acid metabolism triggers mTORC1 activation, which drives glucagon production.Diabetologia · 2023Article
- Advanced Delivery Strategies for Immunotherapy in Type I Diabetes Mellitus.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Review
- Effects of gradient high-field static magnetic fields on diabetic mice.Zoological research · 2023Article
- Alterations in the "Gut-Liver Axis" on Rats with Immunological Hepatic Fibrosis.Journal of immunology research · 2023Article
- Misrouting of glucagon and stathmin-2 towards lysosomal system of α-cells in glucagon hypersecretion of diabetes.Islets · 2022Article
- The past, present, and future physiology and pharmacology of glucagon.Cell metabolism · 2022Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
aims/hypothesisThis study aimed to elucidate the mechanism of increased proliferation of alpha cells in recent-onset type 1 diabetes. Pancreatic beta cells express GAD and produce γ-aminobutyric acid (GABA), which inhibits alpha cell secretion of glucagon. We explored the roles of GABA in alpha cell proliferation in conditions corresponding to type 1 diabetes in a mouse model and in vitro.
methodsType 1 diabetes was induced by injecting the mice with streptozotocin (STZ). Some of the STZ-injected mice were treated with GABA (10 mg/kg daily) for 12 days. Isolated pancreatic islets were treated with STZ or STZ together with GABA for 2 days. The effects of GABA treatment on STZ-induced alpha cell proliferation in vivo and in vitro were assessed. The effect of muscimol, a GABA receptor agonist, on αTC1-6 cell proliferation was also examined.
resultsSTZ injection substantially decreased levels of GAD, GABA and insulin in pancreatic beta cells 12 h after injection; this was followed by an upsurge of phosphorylated mechanistic target of rapamycin (p-mTOR) in the alpha cells at day 1, and a significant increase in alpha cell mass at day 3. Treating STZ-injected mice with GABA largely restored the immunodetectable levels of insulin and GAD in the beta cells and significantly decreased the number of aldehyde dehydrogenase 1 family, member A3 (ALDH1a3)-positive cells, alpha cell mass and hyperglucagonaemia. STZ treatment also increased alpha cell proliferation in isolated islets, which was reversed by co-treatment with GABA. Muscimol, together with insulin, significantly lowered the level of cytosolic Ca CONCLUSIONS/
interpretationGABA signalling critically controls the alpha cell population in pancreatic islets. Low intraislet GABA may contribute to alpha cell hyperplasia in early type 1 diabetes.
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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.