ArticleProceedings of the National Academy of Sciences of the United States of America2015
Glucagon receptor antibody completely suppresses type 1 diabetes phenotype without insulin by disrupting a novel diabetogenic pathway.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 112 citations in OpenAlex.
- Population Pharmacokinetic/Pharmacodynamic Modeling of Volagidemab, a Glucagon Receptor Antagonist, in Healthy Chinese and US Subjects Following Single Subcutaneous Administration.Pharmaceutical research · 2026Trial
- A randomized trial of oral gamma aminobutyric acid (GABA) or the combination of GABA with glutamic acid decarboxylase (GAD) on pancreatic islet endocrine function in children with newly diagnosed type 1 diabetes.Nature communications · 2022Trial
- Glucagon receptor antagonist volagidemab in type 1 diabetes: a 12-week, randomized, double-blind, phase 2 trial.Nature medicine · 2022Trial
- Effect of a glucagon receptor antibody (REMD-477) in type 1 diabetes: A randomized controlled trial.Diabetes, obesity & metabolism · 2018Trial
- Glucagon receptor blockade protects spermatogenesis by enhancing PFKFB3-mediated lactate production in Sertoli cells.Journal of translational medicine · 2026Article
- Glucagon receptor signaling is indispensable for the healthspan effects of caloric restriction in aging male mice.GeroScience · 2026Article
- Regulation of Type 1 Diabetes via Brown Adipocyte-Secreted Proteins and the Novel Glucagon Regulator Nidogen-2.Diabetes · 2025Article
- Case-based learning: a case of maturity-onset diabetes of the young 5 (MODY5) due to 17q12 microdeletion with a diminished plasma glucagon level.Diabetology international · 2025Article
- 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
- Disease-modifying pharmacological treatments of type 1 diabetes: Molecular mechanisms, target checkpoints, and possible combinatorial treatments.Pharmacological reviews · 2025Review
- Pancreatic endocrine and exocrine signaling and crosstalk in physiological and pathological status.Signal transduction and targeted therapy · 2025Review
- Article
- Regulated and adaptive in vivo insulin secretion from islets only containing β-cells.Nature metabolism · 2024Article
- The Inferential Binding Sites of GCGR for Small Molecules Using Protein Dynamic Conformations and Crystal Structures.International journal of molecular sciences · 2024Article
- Review
- The impact of glucagon to support postabsorptive glucose flux and glycemia in healthy rats and its attenuation in male Zucker diabetic fatty rats.American journal of physiology. Endocrinology and metabolism · 2024Article
- An orally available compound suppresses glucagon hypersecretion and normalizes hyperglycemia in type 1 diabetes.JCI insight · 2024Article
- Abnormal late postprandial glucagon response in type 1 diabetes is a function of differences in stimulated C-peptide concentrations.Frontiers in endocrinology · 2024Article
- Structure, function and drug discovery of GPCR signaling.Molecular biomedicine · 2023Review
- Hyperglucagonaemia in diabetes: altered amino acid metabolism triggers mTORC1 activation, which drives glucagon production.Diabetologia · 2023Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
Insulin monotherapy can neither maintain normoglycemia in type 1 diabetes (T1D) nor prevent the long-term damage indicated by elevated glycation products in blood, such as glycated hemoglobin (HbA1c). Here we find that hyperglycemia, when unaccompanied by an acute increase in insulin, enhances itself by paradoxically stimulating hyperglucagonemia. Raising glucose from 5 to 25 mM without insulin enhanced glucagon secretion ∼two- to fivefold in InR1-G9 α cells and ∼18-fold in perfused pancreata from insulin-deficient rats with T1D. Mice with T1D receiving insulin treatment paradoxically exhibited threefold higher plasma glucagon during hyperglycemic surges than during normoglycemic intervals. Blockade of glucagon action with mAb Ac, a glucagon receptor (GCGR) antagonizing antibody, maintained glucose below 100 mg/dL and HbA1c levels below 4% in insulin-deficient mice with T1D. In rodents with T1D, hyperglycemia stimulates glucagon secretion, up-regulating phosphoenolpyruvate carboxykinase and enhancing hyperglycemia. GCGR antagonism in mice with T1D normalizes glucose and HbA1c, even without insulin.
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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 OpenQuestion graph.