ArticleDiabetologia2006
Gamma-aminobutyric acid up- and downregulates insulin secretion from beta cells in concert with changes in glucose concentration.
Article in Diabetologia, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 115 citations in OpenAlex.
- Impact of short-term treatment with benzodiazepines and imidazopyridines on glucose metabolism in healthy subjects.Journal of endocrinological investigation · 2014Trial
- Effects of medetomidine and midazolam alone or in combination on the metabolic and neurohormonal responses in healthy cats.Canadian journal of veterinary research = Revue canadienne de recherche veterinaire · 2008Trial
- Biosensor cell array reveals temporal GABA secretion dynamics from pancreatic islets.Molecular metabolism · 2026Article
- Supplementation of γ-Aminobutyric Acid as a Functional Nutrient.Nutrients · 2026Review
- Purification and Characterization of Gamma-Aminobutyric Acid (GABA) from E. faecium BS5 and Its Antidiabetic Efficacy in Streptozotocin-Induced Diabetic Rats.Probiotics and antimicrobial proteins · 2026Article
- GABA Enhances Growth Hormone Expression by Modulating Somatotroph Pit-1 Transcription via Activation of Calmodulin-Dependent Kinases.Nutrients · 2026Article
- Beta cell secreted GABA sets appropriate insulin secretion by modulating islet calcium oscillations.Molecular metabolism · 2025Article
- Expediting multiple biological properties of main bioactive compounds of Mentha pulegium L.AMB Express · 2025Article
- Article
- Neuronal Nitric Oxide Synthase Regulates Cerebellar Parallel Fiber Slow EPSC in Purkinje Neurons by Modulating STIM1-Gated TRPC3-Containing Channels.Cerebellum (London, England) · 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
- GABA signalling in human pancreatic islets.Frontiers in endocrinology · 2023Review
- Intermittent Hypoxia Interferes with Autocrine Effects of GABA on Insulin Secretion in Postnatal Rodents-Implications for Pediatric Obstructive Sleep Apnea.Children (Basel, Switzerland) · 2022Article
- Autoantibodies directed against glutamate decarboxylase interfere with glucose-stimulated insulin secretion in dispersed rat islets.International journal of experimental pathology · 2022Article
- Specific Expression of KCC2 in the α Cells of Normal and Type 1 Diabetes Model Mouse Pancreatic Islets.Acta histochemica et cytochemica · 2022Article
- Potential Therapeutic Targeting Neurotransmitter Receptors in Diabetes.Frontiers in endocrinology · 2022Review
- The role of GABA in islet function.Frontiers in endocrinology · 2022Review
- Steroids, steroid associated substances and gestational diabetes mellitus.Physiological research · 2021Review
- Altered Steroidome in Women with Gestational Diabetes Mellitus: Focus on Neuroactive and Immunomodulatory Steroids from the 24th Week of Pregnancy to Labor.Biomolecules · 2021Article
- Targeted metabolomic analysis identifies increased serum levels of GABA and branched chain amino acids in canine diabetes.Metabolomics : Official journal of the Metabolomic Society · 2021Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisThe role of gamma-aminobutyric acid (GABA) and A-type GABA receptors (GABA(A)Rs) in modulating islet endocrine function has been actively investigated since the identification of GABA and GABA(A)Rs in the pancreatic islets. However, the reported effects of GABA(A)R activation on insulin secretion from islet beta cells have been controversial.
methodsThis study examined the hypothesis that the effect of GABA on beta cell insulin secretion is dependent on glucose concentration.
resultsPerforated patch-clamp recordings in INS-1 cells demonstrated that GABA, at concentrations ranging from 1 to 1,000 micromol/l, induced a transmembrane current (I(GABA)) which was sensitive to the GABA(A)R antagonist bicuculline. The current-voltage relationship revealed that I(GABA) reversed at -42+/-2.2 mV, independently of glucose concentration. Nevertheless, the glucose concentration critically controlled the membrane potential (V (M)), i.e., at low glucose (0 or 2.8 mmol/l) the endogenous V (M) of INS-1 cells was below the I(GABA) reversal potential and at high glucose (16.7 or 28 mmol/l), the endogenous V (M) of INS-1 cells was above the I(GABA) reversal potential. Therefore, GABA dose-dependently induced membrane depolarisation at a low glucose concentration, but hyperpolarisation at a high glucose concentration. Consistent with electrophysiological findings, insulin secretion assays demonstrated that at 2.8 mmol/l glucose, GABA increased insulin secretion in a dose-dependent fashion (p<0.05, n=7). This enhancement was blocked by bicuculline (p<0.05, n=4). In contrast, in the presence of 28 mmol/l glucose, GABA suppressed the secretion of insulin (p<0.05, n=5). CONCLUSIONS/
interpretationThese findings indicate that activation of GABA(A)Rs in beta cells regulates insulin secretion in concert with changes in glucose levels.
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