ArticleDiabetes2013
Liver-specific disruption of the murine glucagon receptor produces α-cell hyperplasia: evidence for a circulating α-cell growth factor.
Article in Diabetes, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02337660 (Involvement of Steatosis-induced Glucagon Resistance in Hyperglucagonaemia), which is not on this map. Cited by 115 papers, 1 of them a synthesis that pooled it.
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.
Involvement of Steatosis-induced Glucagon Resistance in Hyperglucagonaemia
Who cites it
115 citing papers in PubMed, 1 synthesis or guideline pooled it, 213 citations in OpenAlex.
- The relationship between glucose and the liver-alpha cell axis - A systematic review.Frontiers in endocrinology · 2022Pooled it
- Adrenal hormones in the maintenance of glucose homeostasis during prolonged fasting in male glucagon-deficient mice.Journal of diabetes investigation · 2026Article
- Dietary protein governs the role of insulin signaling in the postprandial regulation of hepatic mTORC1.Nature communications · 2026Article
- Alpha-cell glucagon is essential for maintaining β-cell function and identity in adult mice.The Journal of biological chemistry · 2026Article
- Targeting glucagon signaling in metabolic disorders, functional insights from zebrafish receptor knockouts.Cellular and molecular life sciences : CMLS · 2026Article
- Pancreatic islet α cell function and proliferation require the arginine transporter SLC7A2.The Journal of clinical investigation · 2026Article
- Article
- The expanding landscape of the glucagon signaling network: mechanisms and outcomes.Endocrinology · 2026Review
- GCGR agonism requires GABAergic signaling in the medial basal hypothalamus to promote weight loss in obese mice.Molecular metabolism · 2026Article
- SEL1L-HRD1 ER-associated degradation facilitates prohormone convertase 2 maturation and glucagon production in islet α cells.Nature communications · 2026Article
- Glucagon receptor signaling is indispensable for the healthspan effects of caloric restriction in aging male mice.GeroScience · 2026Article
- Islet hormones at the intersection of glucose and amino acid metabolism.Nature reviews. Endocrinology · 2025Review
- Hepatic PKA Mediates Liver and Pancreatic α-Cell Cross Talk.Diabetes · 2025Article
- Activin B improves glucose metabolism via induction of Fgf21 and hepatic glucagon resistance.Nature communications · 2025Article
- The neglected PCK1/glucagon (inter)action in nutrient homeostasis beyond gluconeogenesis: Disease pathogenesis and treatment.Molecular metabolism · 2025Review
- Flycodes enable simultaneous preclinical analysis for dozens of antibodies in single cassette-dosed mice.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Liver-specific glucagon dysfunction promotes PP-cell hyperplasia and formation of glucagon and PP double-positive cells.PloS one · 2025Article
- TOX4 Inhibition in Chronic Hyperglycemia: Effects on Glycation Stress, Hepatic Protection, Epigenetic Mechanisms, Signaling Pathways, and Beta Cell Dynamics.Current drug metabolism · 2025Review
- Article
- Interruption of glucagon signaling augments islet non-alpha cell proliferation in SLC7A2- and mTOR-dependent manners.Molecular metabolism · 2024Article
55 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
11 authors at 5 institutions in 2 countries.
Funding
Abstract
Glucagon is a critical regulator of glucose homeostasis; however, mechanisms regulating glucagon action and α-cell function and number are incompletely understood. To elucidate the role of the hepatic glucagon receptor (Gcgr) in glucagon action, we generated mice with hepatocyte-specific deletion of the glucagon receptor. Gcgr(Hep)(-/-) mice exhibited reductions in fasting blood glucose and improvements in insulin sensitivity and glucose tolerance compared with wild-type controls, similar in magnitude to changes observed in Gcgr(-/-) mice. Despite preservation of islet Gcgr signaling, Gcgr(Hep)(-/-) mice developed hyperglucagonemia and α-cell hyperplasia. To investigate mechanisms by which signaling through the Gcgr regulates α-cell mass, wild-type islets were transplanted into Gcgr(-/-) or Gcgr(Hep)(-/-) mice. Wild-type islets beneath the renal capsule of Gcgr(-/-) or Gcgr(Hep)(-/-) mice exhibited an increased rate of α-cell proliferation and expansion of α-cell area, consistent with changes exhibited by endogenous α-cells in Gcgr(-/-) and Gcgr(Hep)(-/-) pancreata. These results suggest that a circulating factor generated after disruption of hepatic Gcgr signaling can increase α-cell proliferation independent of direct pancreatic input. Identification of novel factors regulating α-cell proliferation and mass may facilitate the generation and expansion of α-cells for transdifferentiation into β-cells and the treatment of diabetes.
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What OpenQuestion holds
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.