Trial reportThe Journal of biological chemistry2013
Regulation of glucagon secretion in normal and diabetic human islets by γ-hydroxybutyrate and glycine.
Trial report in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
69 citing papers in PubMed, 106 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
- Dorzagliatin in drug-naïve patients with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 3 trial.Nature medicine · 2022Trial
- Stathmin-2 mediates paracrine hormone regulation of glucagon through lysosomal trafficking in αTC1-6 cells.The Journal of physiology · 2026Article
- Noncoding Variants in Intron 2 of HK1 Associated With Hyperinsulinism With Variable Clinical Phenotype.The Journal of clinical endocrinology and metabolism · 2026Article
- Functional evaluation of pancreatic islets from patients with Beckwith-Wiedemann syndrome and congenital hyperinsulinism.The Journal of clinical endocrinology and metabolism · 2026Article
- Article
- Review
- Molecular correlates of glycine receptor activity in human β cells.Molecular metabolism · 2025Article
- Amino acid sensing by the α-cell mitochondrial phosphoenolpyruvate cycle regulates intracellular CabioRxiv : the preprint server for biology · 2025Article
- E3 ligase substrate adaptor SPOP fine-tunes the UPR of pancreatic β cells.Genes & development · 2025Article
- Comparison between capillary electrophoresis and fluorescence anisotropy competitive immunoassay for glucagon.Electrophoresis · 2024Article
- Leucine Suppresses α-Cell cAMP and Glucagon Secretion via a Combination of Cell-Intrinsic and Islet Paracrine Signaling.Diabetes · 2024Article
- Clinical investigation of glucokinase activators for the restoration of glucose homeostasis in diabetes.Journal of diabetes · 2024Review
- The role of GABA in type 1 diabetes.Frontiers in endocrinology · 2024Review
- Global and Spatial Metabolomics of Individual Cells Using a Tapered Pneumatically Assisted nano-DESI Probe.Journal of the American Society for Mass Spectrometry · 2023Article
- Glucokinase and glucokinase activator.Life metabolism · 2023Review
- α-cell electrophysiology and the regulation of glucagon secretion.The Journal of endocrinology · 2023Review
- Progress in genetics of type 2 diabetes and diabetic complications.Journal of diabetes investigation · 2023Review
- A phase I open-label clinical trial to study drug-drug interactions of Dorzagliatin and Sitagliptin in patients with type 2 diabetes and obesity.Nature communications · 2023Article
- Monitoring hormone and small molecule secretion dynamics from islets-on-chip.Analytical and bioanalytical chemistry · 2023Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
Abstract
Paracrine signaling between pancreatic islet β-cells and α-cells has been proposed to play a role in regulating glucagon responses to elevated glucose and hypoglycemia. To examine this possibility in human islets, we used a metabolomic approach to trace the responses of amino acids and other potential neurotransmitters to stimulation with [U-(13)C]glucose in both normal individuals and type 2 diabetics. Islets from type 2 diabetics uniformly showed decreased glucose stimulation of insulin secretion and respiratory rate but demonstrated two different patterns of glucagon responses to glucose: one group responded normally to suppression of glucagon by glucose, but the second group was non-responsive. The non-responsive group showed evidence of suppressed islet GABA levels and of GABA shunt activity. In further studies with normal human islets, we found that γ-hydroxybutyrate (GHB), a potent inhibitory neurotransmitter, is generated in β-cells by an extension of the GABA shunt during glucose stimulation and interacts with α-cell GHB receptors, thus mediating the suppressive effect of glucose on glucagon release. We also identified glycine, acting via α-cell glycine receptors, as the predominant amino acid stimulator of glucagon release. The results suggest that glycine and GHB provide a counterbalancing receptor-based mechanism for controlling α-cell secretory responses to metabolic fuels.
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What OpenQuestion holds
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.