ArticleProceedings of the National Academy of Sciences of the United States of America2012
Metabolic manifestations of insulin deficiency do not occur without glucagon action.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 150 citations in OpenAlex.
- Glucagon receptor signaling is indispensable for the healthspan effects of caloric restriction in aging male mice.GeroScience · 2026Article
- Specific Glucagon Assay System Using a Receptor-Derived Glucagon-Binding Peptide Probe.International journal of molecular sciences · 2026Article
- Glucagon in Pediatric Metabolic Disorders: Pathophysiology and Therapeutic Perspectives.Pediatric reports · 2025Review
- Pancreatic endocrine and exocrine signaling and crosstalk in physiological and pathological status.Signal transduction and targeted therapy · 2025Review
- 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
- Mammalian models of diabetes mellitus, with a focus on type 2 diabetes mellitus.Nature reviews. Endocrinology · 2023Review
- Beta Cell Dysfunction in Youth- and Adult-Onset Type 2 Diabetes: An Extensive Narrative Review with a Special Focus on the Role of Nutrients.Nutrients · 2023Review
- Specific reprogramming of alpha cells to insulin-producing cells by short glucagon promoter-driven Pdx1 and MafA.Molecular therapy. Methods & clinical development · 2023Article
- The placental vasculature is affected by changes in gene expression and glycogen-rich cells in a diet-induced obesity mouse model.PloS one · 2023Article
- Importance of multiple endocrine cell types in islet organoids for type 1 diabetes treatment.Translational research : the journal of laboratory and clinical medicine · 2022Review
- Sustained glucagon receptor antagonism in insulin-deficient high-fat-fed mice.The Journal of endocrinology · 2022Article
- The past, present, and future physiology and pharmacology of glucagon.Cell metabolism · 2022Review
- Review
- Glucagon, cyclic AMP, and hepatic glucose mobilization: A half-century of uncertainty.Physiological reports · 2022Review
- Mediators of Amylin Action in Metabolic Control.Journal of clinical medicine · 2022Review
- Protein Kinase C (Pkc)-δ Mediates Arginine-Induced Glucagon Secretion in Pancreatic α-Cells.International journal of molecular sciences · 2022Article
- Role of Glucagon and Its Receptor in the Pathogenesis of Diabetes.Frontiers in endocrinology · 2022Review
- Drug Discovery of Plausible Lead Natural Compounds That Target the Insulin Signaling Pathway: Bioinformatics Approaches.Evidence-based complementary and alternative medicine : eCAM · 2022Review
- Comparative effects of metformin and Cistus laurifolius L. extract in streptozotocin-induced diabetic rat model: oxidative, inflammatory, apoptotic, and histopathological analyzes.Environmental science and pollution research international · 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
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
To determine unambiguously if suppression of glucagon action will eliminate manifestations of diabetes, we expressed glucagon receptors in livers of glucagon receptor-null (GcgR(-/-)) mice before and after β-cell destruction by high-dose streptozotocin. Wild type (WT) mice developed fatal diabetic ketoacidosis after streptozotocin, whereas GcgR(-/-) mice with similar β-cell destruction remained clinically normal without hyperglycemia, impaired glucose tolerance, or hepatic glycogen depletion. Restoration of receptor expression using adenovirus containing the GcgR cDNA restored hepatic GcgR, phospho-cAMP response element binding protein (P-CREB), and phosphoenol pyruvate carboxykinase, markers of glucagon action, rose dramatically and severe hyperglycemia appeared. When GcgR mRNA spontaneously disappeared 7 d later, P-CREB declined and hyperglycemia disappeared. In conclusion, the metabolic manifestations of diabetes cannot occur without glucagon action and, once present, disappear promptly when glucagon action is abolished. Glucagon suppression should be a major therapeutic goal in diabetes.
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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.