ArticleMolecular metabolism2018
Chronic d-serine supplementation impairs insulin secretion.
Article in Molecular metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 40 citations in OpenAlex.
- d-amino acids: new functional insights.The FEBS journal · 2025Review
- Role of d-serine in intestinal ROS accumulation after sleep deprivation.Science advances · 2025Article
- Dysfunction of the NMDA Receptor in the Pathophysiology of Schizophrenia and/or the Pathomechanisms of Treatment-Resistant Schizophrenia.Biomolecules · 2024Review
- Serum dysregulation of serine and glycine metabolism as predictive biomarker for cognitive decline in frail elderly subjects.Translational psychiatry · 2024Article
- Article
- D-aspartate stimulates growth hormone secretion in wethers.Journal of animal science · 2024Article
- New Therapeutic Targets and Drugs for Schizophrenia Beyond Dopamine D2 Receptor Antagonists.Neuropsychiatric disease and treatment · 2024Review
- Analysis of D-amino acids secreted from murine islets of Langerhans using Marfey's reagent and reversed phase LC-MS/MS.Journal of chromatography. B, Analytical technologies in the biomedical and life sciences · 2023Article
- Potential Therapies Targeting the Metabolic Reprogramming of Diabetes-Associated Breast Cancer.Journal of personalized medicine · 2023Review
- d-Amino Acids and Classical Neurotransmitters in Healthy and Type 2 Diabetes-Affected Human Pancreatic Islets of Langerhans.Metabolites · 2022Article
- L-Serine Supplementation Blunts Fasting-Induced Weight Regain by Increasing Brown Fat Thermogenesis.Nutrients · 2022Article
- Bezafibrate Reduces Elevated Hepatic Fumarate in Insulin-Deficient Mice.Biomedicines · 2022Article
- Integrated Bioinformatics Analysis of Serine Racemase as an Independent Prognostic Biomarker in Endometrial Cancer.Frontiers in genetics · 2022Article
- The neutral amino acid transporter SLC7A10 in adipose tissue, obesity and insulin resistance.Frontiers in cell and developmental biology · 2022Review
- Potential Therapeutic Targeting Neurotransmitter Receptors in Diabetes.Frontiers in endocrinology · 2022Review
- Asc-1 regulates white versus beige adipocyte fate in a subcutaneous stromal cell population.Nature communications · 2021Article
- Article
- D-Serine: A Cross Species Review of Safety.Frontiers in psychiatry · 2021Review
- Exome Sequencing Identifies A Nonsense Variant in DAO Associated With Reduced Energy Expenditure in American Indians.The Journal of clinical endocrinology and metabolism · 2020Article
- Nutritional Characteristics and Functions of D-Amino Acids in the Chicken.The journal of poultry science · 2020Review
Corrections and comments
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Authors and funding
22 authors at 6 institutions in 2 countries.
Funding
Abstract
objectiveThe metabolic role of d-serine, a non-proteinogenic NMDA receptor co-agonist, is poorly understood. Conversely, inhibition of pancreatic NMDA receptors as well as loss of the d-serine producing enzyme serine racemase have been shown to modulate insulin secretion. Thus, we aim to study the impact of chronic and acute d-serine supplementation on insulin secretion and other parameters of glucose homeostasis.
methodsWe apply MALDI FT-ICR mass spectrometry imaging, NMR based metabolomics, 16s rRNA gene sequencing of gut microbiota in combination with a detailed physiological characterization to unravel the metabolic action of d-serine in mice acutely and chronically treated with 1% d-serine in drinking water in combination with either chow or high fat diet feeding. Moreover, we identify SNPs in SRR, the enzyme converting L-to d-serine and two subunits of the NMDA receptor to associate with insulin secretion in humans, based on the analysis of 2760 non-diabetic Caucasian individuals.
resultsWe show that chronic elevation of d-serine results in reduced high fat diet intake. In addition, d-serine leads to diet-independent hyperglycemia due to blunted insulin secretion from pancreatic beta cells. Inhibition of alpha 2-adrenergic receptors rapidly restores glycemia and glucose tolerance in d-serine supplemented mice. Moreover, we show that single nucleotide polymorphisms (SNPs) in SRR as well as in individual NMDAR subunits are associated with insulin secretion in humans.
conclusionThus, we identify a novel role of d-serine in regulating systemic glucose metabolism through modulating insulin secretion.
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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.