ArticleDiabetes2023
Glucagon Acting at the GLP-1 Receptor Contributes to β-Cell Regeneration Induced by Glucagon Receptor Antagonism in Diabetic Mice.
Article in Diabetes, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- GLP-1 receptor agonists and pancreatic beta cell apoptosis in diabetes mellitus: a systematic review and meta-analysis of preclinical studies.Frontiers in clinical diabetes and healthcare · 2025Pooled it
- Design, synthesis and biological evaluation of quinazoline-carbazole derivatives as dual TXNIP/DYRK1A inhibitors for the treatment of type 2 diabetes mellitus.Molecular diversity · 2026Article
- Pancreatic Islet Cell Crosstalk: Insight Into α-/β-Cell Compensatory Mechanisms.Comprehensive Physiology · 2026Article
- Phosphodiesterase ENPP2, which is co-upregulated in obese and pregnant mice, is essential for islet beta cell compensation during obesity.Diabetologia · 2026Article
- Sodium-glucose cotransporter 2 inhibitors facilitate cell phenotype conversion of alpha cells through progenitors to beta cells by activating Ppargc1α in diabetic mice.Chinese medical journal · 2026Article
- GCGR agonism requires GABAergic signaling in the medial basal hypothalamus to promote weight loss in obese mice.Molecular metabolism · 2026Article
- Redosing of anti-CD3 antibodies in NOD mice with new-onset diabetes does not alter the effect of a single treatment course.Diabetologia · 2026Article
- Adaptive mechanisms in pancreatic islets counteract mitochondrial dysfunction in Barth syndrome.Diabetologia · 2026Article
- Berberine: A Rising Star in the Management of Type 2 Diabetes-Novel Insights into Its Anti-Inflammatory, Metabolic, and Epigenetic Mechanisms.Pharmaceuticals (Basel, Switzerland) · 2025Review
- A novel gene therapy platform for the treatment of type 2 diabetes and obesity.Molecular therapy. Nucleic acids · 2025Article
- Application of monoclonal antibodies in diabetes: A bibliometric analysis from 2004-2024.Human vaccines & immunotherapeutics · 2025Article
- Semaglutide Mitigates Ischemic Brain Injury by Inhibiting Ferroptosis via Modulation of FoXO1 and DRP1 Pathways.Molecular neurobiology · 2025Article
- Review
- GLP-1 receptor agonists show no detrimental effect on sperm quality in mouse models and cell lines.Endocrine · 2025Article
- Reprogramming of Different Cell Lineages into Functional β-Cell Substitutes.Cellular reprogramming · 2025Review
- Ginger extract promotes pancreatic islets regeneration in streptozotocin-induced diabetic rats.Bioscience reports · 2025Article
- Harnessing beta-cell replication: advancing molecular insights to regenerative therapies in diabetes.Frontiers in endocrinology · 2025Review
- Intestinal glucagon-like peptide-1 in hypoglycemic counterregulation for type 1 diabetes management.World journal of diabetes · 2024Article
- Interruption of glucagon signaling augments islet non-alpha cell proliferation in SLC7A2- and mTOR-dependent manners.Molecular metabolism · 2024Article
- Decoding the Significance of Alpha Cell Function in the Pathophysiology of Type 1 Diabetes.Cells · 2024Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dysfunction of glucagon-secreting α-cells participates in the progression of diabetes, and glucagon receptor (GCGR) antagonism is regarded as a novel strategy for diabetes therapy. GCGR antagonism upregulates glucagon and glucagon-like peptide 1 (GLP-1) secretion and, notably, promotes β-cell regeneration in diabetic mice. Here, we aimed to clarify the role of GLP-1 receptor (GLP-1R) activated by glucagon and/or GLP-1 in the GCGR antagonism-induced β-cell regeneration. We showed that in db/db mice and type 1 diabetic wild-type or Flox/cre mice, GCGR monoclonal antibody (mAb) improved glucose control, upregulated plasma insulin level, and increased β-cell area. Notably, blockage of systemic or pancreatic GLP-1R signaling by exendin 9-39 (Ex9) or Glp1r knockout diminished the above effects of GCGR mAb. Furthermore, glucagon-neutralizing antibody (nAb), which prevents activation of GLP-1R by glucagon, also attenuated the GCGR mAb-induced insulinotropic effect and β-cell regeneration. In cultured primary mouse islets isolated from normal mice and db/db mice, GCGR mAb action to increase insulin release and to upregulate β-cell-specific marker expression was reduced by a glucagon nAb, by the GLP-1R antagonist Ex9, or by a pancreas-specific Glp1r knockout. These findings suggest that activation of GLP-1R by glucagon participates in β-cell regeneration induced by GCGR antagonism in diabetic mice. ARTICLE HIGHLIGHTS: Glucagon receptor (GCGR) antagonism promotes β-cell regeneration in type 1 and type 2 diabetic mice and in euglycemic nonhuman primates. Glucagon and glucagon-like peptide 1 (GLP-1) can activate the GLP-1 receptor (GLP-1R), and their levels are upregulated following GCGR antagonism. We investigated whether GLP-1R activated by glucagon and/or GLP-1 contributed to β-cell regeneration induced by GCGR antagonism. We found that blockage of glucagon-GLP-1R signaling attenuated the GCGR monoclonal antibody-induced insulinotropic effect and β-cell regeneration in diabetic mice. Our study reveals a novel mechanism of β-cell regeneration and uncovers the communication between α-cells and β-cells in regulating β-cell mass.
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