ArticleeLife2016
Blockade of glucagon signaling prevents or reverses diabetes onset only if residual β-cells persist.
Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 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.
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Who cites it
48 citing papers in PubMed, 71 citations in OpenAlex.
- A first-in-human pharmacodynamic and pharmacokinetic study of a fully human anti-glucagon receptor monoclonal antibody in normal healthy volunteers.Diabetes, obesity & metabolism · 2018Trial
- One Week Exposure to a Somatostatin Receptor 2 Antagonist (SSTR2a) Enhances Glucagon Counterregulation to Insulin-Induced Hypoglycaemia and Does Not Worsen Glycemia in a Male Rat Model of Insulin-Requiring Type 2 Diabetes.Diabetes, obesity & metabolism · 2026Article
- The neglected PCK1/glucagon (inter)action in nutrient homeostasis beyond gluconeogenesis: Disease pathogenesis and treatment.Molecular metabolism · 2025Review
- Interplay Between Insulin Resistance and Immune Dysregulation in Type 2 Diabetes Mellitus: Implications for Therapeutic Interventions.ImmunoTargets and therapy · 2025Review
- Regulated and adaptive in vivo insulin secretion from islets only containing β-cells.Nature metabolism · 2024Article
- Review
- Advances in basic research on glucagon and alpha cells.Diabetology international · 2024Review
- Glucagon resistance and metabolic-associated steatotic liver disease: a review of the evidence.The Journal of endocrinology · 2024Review
- Polyester Nanoparticles with Controlled Topography for Peroral Drug Delivery Using Insulin as a Model Protein.ACS nano · 2024Article
- Rise in fasting and dynamic glucagon levels in children and adolescents with obesity is moderate in subjects with impaired fasting glucose but accentuated in subjects with impaired glucose tolerance or type 2 diabetes.Frontiers in endocrinology · 2024Article
- The role of preproglucagon peptides in regulating β-cell morphology and responses to streptozotocin-induced diabetes.American journal of physiology. Endocrinology and metabolism · 2023Article
- Article
- The past, present, and future physiology and pharmacology of glucagon.Cell metabolism · 2022Review
- Sustained glucagon receptor antagonism in insulin-deficient high-fat-fed mice.The Journal of endocrinology · 2022Article
- Regulation of α-cell glucagon secretion: The role of second messengers.Chronic diseases and translational medicine · 2022Review
- Role of Glucagon and Its Receptor in the Pathogenesis of Diabetes.Frontiers in endocrinology · 2022Review
- A neural basis for brain leptin action on reducing type 1 diabetic hyperglycemia.Nature communications · 2021Article
- Glucagon blockade restores functional β-cell mass in type 1 diabetic mice and enhances function of human islets.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Glucagon Resistance and Decreased Susceptibility to Diabetes in a Model of Chronic Hyperglucagonemia.Diabetes · 2021Article
- Pathways of Glucagon Secretion and Trafficking in the Pancreatic Alpha Cell: Novel Pathways, Proteins, and Targets for Hyperglucagonemia.Frontiers in endocrinology · 2021Review
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Authors and funding
7 authors at 5 institutions in 3 countries.
Funding
Abstract
Glucagon secretion dysregulation in diabetes fosters hyperglycemia. Recent studies report that mice lacking glucagon receptor (Gcgr(-/-)) do not develop diabetes following streptozotocin (STZ)-mediated ablation of insulin-producing β-cells. Here, we show that diabetes prevention in STZ-treated Gcgr(-/-) animals requires remnant insulin action originating from spared residual β-cells: these mice indeed became hyperglycemic after insulin receptor blockade. Accordingly, Gcgr(-/-) mice developed hyperglycemia after induction of a more complete, diphtheria toxin (DT)-induced β-cell loss, a situation of near-absolute insulin deficiency similar to type 1 diabetes. In addition, glucagon deficiency did not impair the natural capacity of α-cells to reprogram into insulin production after extreme β-cell loss. α-to-β-cell conversion was improved in Gcgr(-/-) mice as a consequence of α-cell hyperplasia. Collectively, these results indicate that glucagon antagonism could i) be a useful adjuvant therapy in diabetes only when residual insulin action persists, and ii) help devising future β-cell regeneration therapies relying upon α-cell reprogramming.
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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.