ArticleCell metabolism2017
Interrupted Glucagon Signaling Reveals Hepatic α Cell Axis and Role for L-Glutamine in α Cell Proliferation.
Article in Cell metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 144 papers, 1 of them a synthesis that pooled it.
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Who cites it
144 citing papers in PubMed, 1 synthesis or guideline pooled it, 207 citations in OpenAlex.
- The relationship between glucose and the liver-alpha cell axis - A systematic review.Frontiers in endocrinology · 2022Pooled it
- Hepatic steatosis in humans is associated with preserved glucagon action on amino acid metabolism.The Journal of clinical investigation · 2026Trial
- Adrenal hormones in the maintenance of glucose homeostasis during prolonged fasting in male glucagon-deficient mice.Journal of diabetes investigation · 2026Article
- mNature metabolism · 2026Article
- Loss of Slc39a5 in α-cells impairs glucose metabolism by chronically increasing glucagon.Journal of advanced research · 2026Article
- Pancreatic islet α cell function and proliferation require the arginine transporter SLC7A2.The Journal of clinical investigation · 2026Article
- Inter-organ metabolic feedback via BCAA catabolism regulates glucagon-like hormone secretion in Drosophila.Nature communications · 2026Article
- Endocrine regulation of the hepatic fasting response: cues, cooperation and consequences.Nature reviews. Endocrinology · 2026Review
- Article
- CBP/p300 is critical for the expansion and maintenance of functional pancreatic α cell mass.Nature communications · 2026Article
- The expanding landscape of the glucagon signaling network: mechanisms and outcomes.Endocrinology · 2026Review
- Impact of obesity on aromatic amino acids and brain glucose during acute hyperglycemia.American journal of physiology. Endocrinology and metabolism · 2026Article
- Article
- SEL1L-HRD1 ER-associated degradation facilitates prohormone convertase 2 maturation and glucagon production in islet α cells.Nature communications · 2026Article
- In vivo functional profiling and structural characterization of the humanScience advances · 2026Article
- α-cell SLC38A5 supports amino acid-induced α-cell proliferation and glucagon secretion.Frontiers in endocrinology · 2026Article
- hLMR1, a hepatocyte-specific long noncoding RNA that represses amino acid catabolism through pre-mRNA interaction in human liver.PloS one · 2026Article
- Beyond Discrete Diagnoses: Conceptualizing Obesity-associated Metabolic Disorders as a Unified, Dynamic Continuum.Current obesity reports · 2025Review
- Hepatic CBP/p300 Orchestrate Amino Acid-Driven Gluconeogenesis through Histone Crotonylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Bridging pancreatic and hepatic development: overlapping genes and their role in diabetes.Cellular & molecular biology letters · 2025Review
84 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
28 authors at 7 institutions in 2 countries.
Funding
Abstract
Decreasing glucagon action lowers the blood glucose and may be useful therapeutically for diabetes. However, interrupted glucagon signaling leads to α cell proliferation. To identify postulated hepatic-derived circulating factor(s) responsible for α cell proliferation, we used transcriptomics/proteomics/metabolomics in three models of interrupted glucagon signaling and found that proliferation of mouse, zebrafish, and human α cells was mTOR and FoxP transcription factor dependent. Changes in hepatic amino acid (AA) catabolism gene expression predicted the observed increase in circulating AAs. Mimicking these AA levels stimulated α cell proliferation in a newly developed in vitro assay with L-glutamine being a critical AA. α cell expression of the AA transporter Slc38a5 was markedly increased in mice with interrupted glucagon signaling and played a role in α cell proliferation. These results indicate a hepatic α islet cell axis where glucagon regulates serum AA availability and AAs, especially L-glutamine, regulate α cell proliferation and mass via mTOR-dependent nutrient sensing.
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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.