ArticleCell reports2021
Hepatocyte membrane potential regulates serum insulin and insulin sensitivity by altering hepatic GABA release.
Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- A critical role of hepatic GABA in the metabolic dysfunction and hyperphagia of obesity.Cell reports · 2021Trial
- Hepatic neurons and metabolically induced liver dysfunction.Nature reviews. Endocrinology · 2026Review
- Peripheral GABA Signaling in Metabolic Adaptation and Maladaptation.International journal of molecular sciences · 2026Review
- Supplementation of γ-Aminobutyric Acid as a Functional Nutrient.Nutrients · 2026Review
- Vagal GABAergic signaling in autonomic control of cardiometabolic function.American journal of physiology. Cell physiology · 2026Review
- Liver-pancreas communication in disease and drug development.Acta pharmaceutica Sinica. B · 2026Review
- Mechanistic insights into the liver-brain axis during chronic liver disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Gut-brain communication: Functional anatomy of vagal afferents.Current opinion in neurobiology · 2025Review
- Reduced liver mitochondrial energy metabolism impairs food intake regulation following gastric preloads and fasting.Molecular metabolism · 2025Article
- Potential bidirectional communication between the liver and the central circadian clock in MASLD.npj metabolic health and disease · 2025Review
- Hepatic vagal afferents convey clock-dependent signals to regulate circadian food intake.Science (New York, N.Y.) · 2024Article
- Type 2 diabetes mellitus in adults: pathogenesis, prevention and therapy.Signal transduction and targeted therapy · 2024 · on this mapReview
- Circadian Regulation of the Lactate Metabolic Kinetics in Mice Using the [Molecular neurobiology · 2024Article
- Hepatic interoception in health and disease.Autonomic neuroscience : basic & clinical · 2024Review
- Hepatic Global Transcriptomic Profiles of Holstein Cows According to Parity Reveal Age-Related Changes in Early Lactation.International journal of molecular sciences · 2023Article
- Review
- Gamma-Aminobutyric Acid Signaling in Damage Response, Metabolism, and Disease.International journal of molecular sciences · 2023Review
- Reduced Liver-Specific PGC1a Increases Susceptibility for Short-Term Diet-Induced Weight Gain in Male Mice.Nutrients · 2021Article
- Study on the Effects of Chinese Materia Medica Processing on the Hypoglycemic Activity and Chemical Composition of Anemarrhenae Rhizoma.Evidence-based complementary and alternative medicine : eCAM · 2021Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Hepatic lipid accumulation in obesity correlates with the severity of hyperinsulinemia and systemic insulin resistance. Obesity-induced hepatocellular lipid accumulation results in hepatocyte depolarization. We have established that hepatocyte depolarization depresses hepatic afferent vagal nerve firing, increases GABA release from liver slices, and causes hyperinsulinemia. Preventing hepatic GABA release or eliminating the ability of the liver to communicate to the hepatic vagal nerve ameliorates the hyperinsulinemia and insulin resistance associated with diet-induced obesity. In people with obesity, hepatic expression of GABA transporters is associated with glucose infusion and disposal rates during a hyperinsulinemic euglycemic clamp. Single-nucleotide polymorphisms in hepatic GABA re-uptake transporters are associated with an increased incidence of type 2 diabetes mellitus. Herein, we identify GABA as a neuro-hepatokine that is dysregulated in obesity and whose release can be manipulated to mute or exacerbate the glucoregulatory dysfunction common to obesity.
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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.