ArticleThe Journal of clinical investigation2026
Pancreatic islet α cell function and proliferation require the arginine transporter SLC7A2.
Article in The Journal of clinical investigation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- mNature metabolism · 2026Article
- scMapNet: Marker-based cell type annotation of scRNA-seq data via vision transfer learning with tabular-to-image transformations.Journal of advanced research · 2026Article
- Article
- The Response of Alpha-Aminoadipic Acid (2-AAA) to Short Term Lysine Ingestion in Healthy Individuals.Endocrinology, diabetes & metabolism · 2026Article
- α-cell SLC38A5 supports amino acid-induced α-cell proliferation and glucagon secretion.Frontiers in endocrinology · 2026Article
- Editorial: Mechanisms of endocrine cell proliferation in the embryonic, neonatal and adult pancreas.Frontiers in endocrinology · 2026Article
- Hepatic PKA Mediates Liver and Pancreatic α-Cell Cross Talk.Diabetes · 2025Article
- Amino acid sensing by the α-cell mitochondrial phosphoenolpyruvate cycle regulates intracellular CabioRxiv : the preprint server for biology · 2025Article
- The role of MKI67 in the regulation of 60S pre-ribosome nucleolar export, transcripts, energy supply, and apoptosis.bioRxiv : the preprint server for biology · 2025Article
- Parallel measurement of transcriptomes and proteomes from same single cells using nanodroplet splitting.Nature communications · 2024Article
- Interruption of glucagon signaling augments islet non-alpha cell proliferation in SLC7A2- and mTOR-dependent manners.Molecular metabolism · 2024Article
- Systemic inhibition ofbioRxiv : the preprint server for biology · 2024Article
- Interruption of glucagon signaling augments islet non-alpha cell proliferation in SLC7A2- and mTOR-dependent manners.bioRxiv : the preprint server for biology · 2024Article
- ErbB3 is required for hyperaminoacidemia-induced pancreatic α cell hyperplasia.The Journal of biological chemistry · 2024Article
- α-methyltryptophan-mediated protection against diabetic nephropathy inFrontiers in pharmacology · 2024Article
- Metabolic regulation of glucagon secretion.The Journal of endocrinology · 2023Article
Corrections and comments
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Authors and funding
22 authors.
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Abstract
Interrupting glucagon signaling decreases gluconeogenesis and the fractional extraction of amino acids by liver from blood, resulting in lower glycemia. The resulting hyperaminoacidemia stimulates α cell proliferation and glucagon secretion via a liver/α cell axis. We hypothesized that α cells detect and respond to circulating amino acids' levels via a unique amino acid transporter repertoire. We found that Slc7a2/SLC7A2 is the most highly expressed cationic amino acid transporter in α cells, with its expression being 3-fold greater in α than β cells in both mouse and human. Employing cell culture, zebrafish, and knockout mouse models, we found that the cationic amino acid arginine and SLC7A2 are required for α cell proliferation in response to interrupted glucagon signaling. Ex vivo and in vivo assessment of islet function in Slc7a2-/- mice showed decreased arginine-stimulated glucagon and insulin secretion. We found that arginine activation of mTOR signaling and induction of the glutamine transporter SLC38A5 was dependent on SLC7A2, showing that the role of both in α cell proliferation is dependent on arginine transport and SLC7A2. Finally, we identified single nucleotide polymorphisms in SLC7A2 associated with HbA1c. Together, these data indicate a central role for SLC7A2 in amino acid-stimulated α cell proliferation and islet hormone secretion.
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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 Socratic graph.