ArticleDiabetes2015
EphA4 Receptor Forward Signaling Inhibits Glucagon Secretion From α-Cells.
Article in Diabetes, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed.
- Unraveling enteroendocrine cell lineage dynamics and associated gene regulatory networks during intestinal development.Biology open · 2025Article
- Scaffold-free endocrine tissue engineering: role of islet organization and implications in type 1 diabetes.BMC endocrine disorders · 2025Review
- The Discovery and Characterization of a Potent DPP-IV Inhibitory Peptide from Oysters for the Treatment of Type 2 Diabetes Based on Computational and Experimental Studies.Marine drugs · 2024Article
- An orally available compound suppresses glucagon hypersecretion and normalizes hyperglycemia in type 1 diabetes.JCI insight · 2024Article
- Eph receptors and ephrins in cancer progression.Nature reviews. Cancer · 2024Review
- Vascular endothelial growth factor B improves impaired glucose tolerance through insulin-mediated inhibition of glucagon secretion.World journal of diabetes · 2023Article
- A Supportive Role of Mesenchymal Stem Cells on Insulin-Producing Langerhans Islets with a Specific Emphasis on The Secretome.Biomedicines · 2023Review
- α-cell electrophysiology and the regulation of glucagon secretion.The Journal of endocrinology · 2023Review
- Not the second fiddle: α cell development, identity, and function in health and diabetes.The Journal of endocrinology · 2023Review
- Disrupted glucose homeostasis and glucagon and insulin secretion defects in Robo βKO mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- The human α cell in health and disease.The Journal of endocrinology · 2023Review
- The EPH/Ephrin System in Pancreatic Ductal Adenocarcinoma (PDAC): From Pathogenesis to Treatment.International journal of molecular sciences · 2023Review
- Article
- Diverse roles for axon guidance pathways in adult tissue architecture and function.Natural sciences (Weinheim, Germany) · 2022Article
- Glucose inhibits glucagon secretion by decreasing [CaMolecular metabolism · 2022Article
- Article
- Axon Guidance Molecules in the Islets of Langerhans.Frontiers in endocrinology · 2022Review
- The physiological role of β-cell heterogeneity in pancreatic islet function.Nature reviews. Endocrinology · 2022Review
- Review
- The Role of the α Cell in the Pathogenesis of Diabetes: A World beyond the Mirror.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
The loss of inhibition of glucagon secretion exacerbates hyperglycemia in type 1 and 2 diabetes. However, the molecular mechanisms that regulate glucagon secretion in unaffected and diabetic states remain relatively unexplained. We present evidence supporting a new model of juxtacrine-mediated regulation of glucagon secretion where neighboring islet cells negatively regulate glucagon secretion through tonic stimulation of α-cell EphA receptors. Primarily through EphA4 receptors, this stimulation correlates with maintenance of a dense F-actin network. In islets, additional stimulation and inhibition of endogenous EphA forward signaling result in inhibition and enhancement, respectively, of glucagon secretion, accompanied by an increase and decrease, respectively, in α-cell F-actin density. Sorted α-cells lack endogenous stimulation of EphA forward signaling from neighboring cells, resulting in enhanced basal glucagon secretion as compared with islets and the elimination of glucose inhibition of glucagon secretion. Restoration of EphA forward signaling in sorted α-cells recapitulates both normal basal glucagon secretion and glucose inhibition of glucagon secretion. Additionally, α-cell-specific EphA4(-/-) mice exhibit abnormal glucagon dynamics, and EphA4(-/-) α-cells contain less dense F-actin networks than EphA4(+/+) α-cells. This juxtacrine-mediated model provides insight into the functional and dysfunctional regulation of glucagon secretion and opens up new therapeutic strategies for the clinical management of 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.