ArticleCells2021
Glucagon Potentiates Insulin Secretion Via β-Cell GCGR at Physiological Concentrations of Glucose.
Article in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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Who cites it
25 citing papers in PubMed, 39 citations in OpenAlex.
- Dose-Response Effect of Glucagon on Glucose, Beta-Cell Secretion and Metabolism in Healthy Individuals.Diabetes, obesity & metabolism · 2026Article
- Article
- Pancreatic Islet Cell Crosstalk: Insight Into α-/β-Cell Compensatory Mechanisms.Comprehensive Physiology · 2026Article
- The expanding landscape of the glucagon signaling network: mechanisms and outcomes.Endocrinology · 2026Review
- Survodutide acts through circumventricular organs in the brain and activates neuronal regions associated with appetite regulation.Molecular metabolism · 2026Article
- Article
- Glucagon in Pediatric Metabolic Disorders: Pathophysiology and Therapeutic Perspectives.Pediatric reports · 2025Review
- Localized GLP1 receptor pre-internalization directs pancreatic alpha cell to beta cell communication.Cell metabolism · 2025Article
- Biphasic glucose-stimulated insulin secretion over decades: a journey from measurements and modeling to mechanistic insights.Life metabolism · 2025Review
- Article
- Review
- Cystic fibrosis-related diabetes is associated with reduced islet protein expression of GLP-1 receptor and perturbation of cell-specific transcriptional programs.Scientific reports · 2024Article
- V1bR enhances glucose-stimulated insulin secretion by paracrine production of glucagon which activates GLP-1 receptor.Cell & bioscience · 2024Article
- Pancreatic beta-cell mass and function and therapeutic implications of using antidiabetic medications in type 2 diabetes.Journal of diabetes investigation · 2024Review
- The Role of G Protein-Coupled Receptors and Receptor Kinases in PancreaticPharmacological reviews · 2024Review
- Readily releasable β cells with tight CaNature metabolism · 2024Article
- Suppression of cAMP/PKA/CREB signaling ameliorates retinal injury in diabetic retinopathy.The Kaohsiung journal of medical sciences · 2023Article
- Noncanonical Regulation of cAMP-Dependent Insulin Secretion and Its Implications in Type 2 Diabetes.Comprehensive Physiology · 2023Article
- Glucagon Acting at the GLP-1 Receptor Contributes to β-Cell Regeneration Induced by Glucagon Receptor Antagonism in Diabetic Mice.Diabetes · 2023Article
- Insights into the Role of Glucagon Receptor Signaling in Metabolic Regulation from Pharmacological Inhibition and Tissue-Specific Knockout Models.Biomedicines · 2022Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Incretin-potentiated glucose-stimulated insulin secretion (GSIS) is critical to maintaining euglycemia, of which GLP-1 receptor (GLP-1R) on β-cells plays an indispensable role. Recently, α-cell-derived glucagon but not intestine-derived GLP-1 has been proposed as the critical hormone that potentiates GSIS via GLP-1R. However, the function of glucagon receptors (GCGR) on β-cells remains elusive. Here, using GCGR or GLP-1R antagonists, in combination with glucagon, to treat single β-cells, α-β cell clusters and isolated islets, we found that glucagon potentiates insulin secretion via β-cell GCGR at physiological but not high concentrations of glucose. Furthermore, we transfected primary mouse β-cells with RAB-ICUE (a genetically encoded cAMP fluorescence indicator) to monitor cAMP level after glucose stimulation and GCGR activation. Using specific inhibitors of different adenylyl cyclase (AC) family members, we revealed that high glucose concentration or GCGR activation independently evoked cAMP elevation via AC5 in β-cells, thus high glucose stimulation bypassed GCGR in promoting insulin secretion. Additionally, we generated β-cell-specific GCGR knockout mice which glucose intolerance was more severe when fed a high-fat diet (HFD). We further found that β-cell GCGR activation promoted GSIS more than GLP-1R in HFD, indicating the critical role of GCGR in maintaining glucose homeostasis during nutrient overload.
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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.