ArticleMolecular metabolism2015
α/β-Hydrolase domain-6 and saturated long chain monoacylglycerol regulate insulin secretion promoted by both fuel and non-fuel stimuli.
Article in Molecular metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Impact of monotherapy and combination therapy with glucagon-like peptide-1 receptor agonists on exosomal and non-exosomal MicroRNA signatures in type 2 diabetes mellitus: a systematic review.Journal of translational medicine · 2025Pooled it
- Effects of fecal microbiota transplant on DNA methylation in subjects with metabolic syndrome.Gut microbesTrial
- Non-enzymatic hepatic ABHD6 interacts with Akt-FoxO1 axis to regulate metabolic health.Nature communications · 2026Article
- Tissue-specific roles of monoacylglycerol (MAG) in metabolic diseases.Immunometabolism (Cobham, Surrey) · 2026Review
- Visceral adiposity, metabolic health and aging.Nature aging · 2026Review
- Non-enzymatic ABHD6 interacts with Akt-FoxO1 axis to regulate selective hepatic insulin resistance.bioRxiv : the preprint server for biology · 2026Article
- Suppression of adipocyte ABHD6 favors anti-inflammatory and adipogenic programs to preserve adipose tissue fitness in obesity.Molecular metabolism · 2025Article
- Chemoproteomics identifies protein ligands for monoacylglycerol lipids.Communications chemistry · 2025Article
- Clinical effectiveness of fecal microbial transplantation for metabolic syndrome: Advances in clinical efficacy and multi-omics research.Current research in microbial sciences · 2025Review
- Promising Inhibitors of Endocannabinoid Degrading Enzymes Sharing a Carbamate Scaffold.Mini reviews in medicinal chemistry · 2025Review
- Evaluating the impact of lipids in isolated islet research.Frontiers in endocrinology · 2025Review
- ABHD6 loss-of-function in mesoaccumbens postsynaptic but not presynaptic neurons prevents diet-induced obesity in male mice.Nature communications · 2024Article
- Fluorescence-Based Enzyme Activity Assay: Ascertaining the Activity and Inhibition of Endocannabinoid Hydrolytic Enzymes.International journal of molecular sciences · 2024Review
- Distribution and Level of Bioactive Monoacylglycerols in 12 Marine Microalgal Species.Marine drugs · 2024Article
- Lipidomic QTL in Diversity Outbred mice identifies a novel function for α/β hydrolase domain 2 (Abhd2) as an enzyme that metabolizes phosphatidylcholine and cardiolipin.PLoS genetics · 2023Article
- Lipidomic QTL in Diversity Outbred mice identifies a novel function for α/β hydrolase domain 2 (bioRxiv : the preprint server for biology · 2023Article
- Review
- Phenotypic Characterization of the Endocannabinoid-Degrading Enzyme Alpha/Beta-Hydrolase Domain 6 Knockout Rat.Cannabis and cannabinoid research · 2022Article
- Hypothalamic endocannabinoids in obesity: an old story with new challenges.Cellular and molecular life sciences : CMLS · 2021Review
- α/β-Hydrolase Domain (ABHD) Inhibitors as New Potential Therapeutic Options against Lipid-Related Diseases.Journal of medicinal chemistry · 2021Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveα/β-Hydrolase domain-6 (ABHD6) is a newly identified monoacylglycerol (MAG) lipase. We recently reported that it negatively regulates glucose stimulated insulin secretion (GSIS) in the β cells by hydrolyzing lipolysis-derived MAG that acts as a metabolic coupling factor and signaling molecule via exocytotic regulator Munc13-1. Whether ABHD6 and MAG play a role in response to all classes of insulin secretagogues, in particular various fuel and non-fuel stimuli, is unknown.
methodsInsulin secretion in response to various classes of secretagogues, exogenous MAG and pharmacological agents was measured in islets of mice deficient in ABHD6 specifically in the β cell (BKO). Islet perifusion experiments and determinations of glucose and fatty acid metabolism, cytosolic Ca(2+) and MAG species levels were carried out.
resultsDeletion of ABHD6 potentiated insulin secretion in response to the fuels glutamine plus leucine and α-ketoisocaproate and to the non-fuel stimuli glucagon-like peptide 1, carbamylcholine and elevated KCl. Fatty acids amplified GSIS in control and BKO mice to the same extent. Exogenous 1-MAG amplified insulin secretion in response to fuel and non-fuel stimuli. MAG hydrolysis activity was greatly reduced in BKO islets without changes in total diacylglycerol and triacylglycerol lipase activity. ABHD6 deletion induced insulin secretion independently from KATP channels and did not alter the glucose induced rise in intracellular Ca(2+). Perifusion studies showed elevated insulin secretion during second phase of GSIS in BKO islets that was not due to altered cytosolic Ca(2+) signaling or because of changes in glucose and fatty acid metabolism. Glucose increased islet saturated long chain 1-MAG species and ABHD6 deletion caused accumulation of these 1-MAG species at both low and elevated glucose.
conclusionABHD6 regulates insulin secretion in response to fuel stimuli at large and some non-fuel stimuli by controlling long chain saturated 1-MAG levels that synergize with other signaling pathways for secretion.
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