ArticleJournal of the Endocrine Society2021
A Metabolomic Signature of Glucagon Action in Healthy Individuals With Overweight/Obesity.
Article in Journal of the Endocrine Society, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03139305 (Effect of Prolonged), which is not on this map. Cited by 15 papers.
What it found
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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.
Effect of Prolonged (72 Hour) Glucagon Administration on Energy Expenditure in Healthy Obese Subjects
Who cites it
15 citing papers in PubMed.
- Dose-Response Effect of Glucagon on Glucose, Beta-Cell Secretion and Metabolism in Healthy Individuals.Diabetes, obesity & metabolism · 2026Article
- Endocrine regulation of the hepatic fasting response: cues, cooperation and consequences.Nature reviews. Endocrinology · 2026Review
- Beyond exercise and appetite: The expanding biology and therapeutic potential of N-lactoyl-phenylalanine.The Journal of pharmacology and experimental therapeutics · 2026Review
- Hepatic PKA Mediates Liver and Pancreatic α-Cell Cross Talk.Diabetes · 2025Article
- The neglected PCK1/glucagon (inter)action in nutrient homeostasis beyond gluconeogenesis: Disease pathogenesis and treatment.Molecular metabolism · 2025Review
- Glucagon, Metabolic Dysfunction-Associated Steatotic Liver Disease and Amino Acids in Humans and Animals without Diabetes Mellitus-An Evidence Map.Life (Basel, Switzerland) · 2024Review
- Glucagon infusion alters the circulating metabolome and urine amino acid excretion in dogs.The Journal of endocrinology · 2024Article
- Glucagon resistance and metabolic-associated steatotic liver disease: a review of the evidence.The Journal of endocrinology · 2024Review
- A review of an investigational drug retatrutide, a novel triple agonist agent for the treatment of obesity.European journal of clinical pharmacology · 2024Review
- Metformin and feeding increase levels of the appetite-suppressing metabolite Lac-Phe in humans.Nature metabolism · 2024Article
- Opposing effects of chronic glucagon receptor agonism and antagonism on amino acids, hepatic gene expression, and alpha cells.iScience · 2022Article
- The Liver-α-Cell Axis in Health and in Disease.Diabetes · 2022Review
- CCDB: A database for exploring inter-chemical correlations in metabolomics and exposomics datasets.Environment international · 2022Article
- Delineating the activation mechanism and conformational landscape of a class B G protein-coupled receptor glucagon receptor.Computational and structural biotechnology journal · 2022Article
- Metabolomic Profiling of Amino Acids in Human Plasma Distinguishes Diabetic Kidney Disease From Type 2 Diabetes Mellitus.Frontiers in medicine · 2021Article
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
contextGlucagon is produced and released from the pancreatic alpha-cell to regulate glucose levels during periods of fasting. The main target for glucagon action is the liver, where it activates gluconeogenesis and glycogen breakdown; however, glucagon is postulated to have other roles within the body.
objectiveWe sought to identify the circulating metabolites that would serve as markers of glucagon action in humans.
methodsIn this study (NCT03139305), we performed a continuous 72-hour glucagon infusion in healthy individuals with overweight/obesity. Participants were randomized to receive glucagon 12.5 ng/kg/min (GCG 12.5), glucagon 25 ng/kg/min (GCG 25), or a placebo control. A comprehensive metabolomics analysis was then performed from plasma isolated at several time points during the infusion to identify markers of glucagon activity.
resultsGlucagon (GCG 12.5 and GCG 25) resulted in significant changes in the plasma metabolome as soon as 4 hours following infusion. Pathways involved in amino acid metabolism were among the most affected. Rapid and sustained reduction of a broad panel of amino acids was observed. Additionally, time-dependent changes in free fatty acids and diacylglycerol and triglyceride species were observed.
conclusionThese results define a distinct signature of glucagon action that is broader than the known changes in glucose levels. In particular, the robust changes in amino acid levels may prove useful to monitor changes induced by glucagon in the context of additional glucagon-like peptide-1 or gastric inhibitory polypeptide treatment, as these agents also elicit changes in glucose levels.
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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.