ReviewFrontiers in endocrinology2022
Alpha-cell paracrine signaling in the regulation of beta-cell insulin secretion.
Review in Frontiers in endocrinology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Current Insights, Advantages and Challenges of Small Molecule Glucagon-like Peptide 1 Receptor Agonists: A Scoping Review.Journal of Brown hospital medicine · 2025Pooled it
- Heterogeneous expression patterns of the T2D-associated kinesin-4 KIF21A in pancreatic islet endocrine cells.Molecular metabolism · 2026Article
- Biological sex affects human islet gene expression and mitochondrial function in type 2 diabetes.Endocrinology · 2026Article
- SEL1L-HRD1 ER-associated degradation facilitates prohormone convertase 2 maturation and glucagon production in islet α cells.Nature communications · 2026Article
- Harnessing Phytochemicals and Nanotechnology Synergy for Molecular, Epigenetic, and Microbiota-Driven Regulation in Type 2 Diabetes Mellitus.Pharmaceutics · 2026Review
- Elucidating the Epigenetic Landscape of Type 2 Diabetes Mellitus: A Multi-Omics Analysis Revealing Novel CpG Sites and Their Association with Cardiometabolic Traits.Diabetes & metabolism journal · 2026Article
- Biological sex affects human islet gene expression and mitochondrial function in type 2 diabetes.bioRxiv : the preprint server for biology · 2025Article
- Review
- Histomorphogenesis of human pancreatic islets amidst maternal anaemia: a critical insight.Anatomy & cell biology · 2025Article
- GLP-1 receptor agonism: a transformative approach for managing type-2 diabetes and obesity.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2025Review
- Localized GLP1 receptor pre-internalization directs pancreatic alpha cell to beta cell communication.Cell metabolism · 2025Article
- Glucagon-like peptide-1.Trends in endocrinology and metabolism: TEM · 2025Article
- Ginger extract promotes pancreatic islets regeneration in streptozotocin-induced diabetic rats.Bioscience reports · 2025Article
- ZHX3 interacts with CEBPB to repress hepatic gluconeogenic gene expression and uric acid secretion.PNAS nexus · 2025Article
- Improved glucose handling in female rat offspring of a hypertensive pregnancy with intrauterine growth restriction.Physiological reports · 2025Article
- Research progress in precision medicine for type 2 diabetes based on the GLP-1.Frontiers in endocrinology · 2025Review
- Quantitative analysis of islet prohormone convertase 1/3 expression in human pancreas donors with diabetes.Diabetologia · 2024Article
- Decoding the Significance of Alpha Cell Function in the Pathophysiology of Type 1 Diabetes.Cells · 2024Review
- 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
- A metabolic dysfunction-associated steatotic liver acinus biomimetic induces pancreatic islet dysfunction in a coupled microphysiology system.Communications biology · 2024Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
As an incretin hormone, glucagon-like peptide 1 (GLP-1) lowers blood glucose levels by enhancing glucose-stimulated insulin secretion from pancreatic beta-cells. Therapies targeting the GLP-1 receptor (GLP-1R) use the classical incretin model as a physiological framework in which GLP-1 secreted from enteroendocrine L-cells acts on the beta-cell GLP-1R. However, this model has come into question, as evidence demonstrating local, intra-islet GLP-1 production has advanced the competing hypothesis that the incretin activity of GLP-1 may reflect paracrine signaling of GLP-1 from alpha-cells on GLP-1Rs on beta-cells. Additionally, recent studies suggest that alpha-cell-derived glucagon can serve as an additional, albeit less potent, ligand for the beta-cell GLP-1R, thereby expanding the role of alpha-cells beyond that of a counterregulatory cell type. Efforts to understand the role of the alpha-cell in the regulation of islet function have revealed both transcriptional and functional heterogeneity within the alpha-cell population. Further analysis of this heterogeneity suggests that functionally distinct alpha-cell subpopulations display alterations in islet hormone profile. Thus, the role of the alpha-cell in glucose homeostasis has evolved in recent years, such that alpha-cell to beta-cell communication now presents a critical axis regulating the functional capacity of beta-cells. Herein, we describe and integrate recent advances in our understanding of the impact of alpha-cell paracrine signaling on insulin secretory dynamics and how this intra-islet crosstalk more broadly contributes to whole-body glucose regulation in health and under metabolic stress. Moreover, we explore how these conceptual changes in our understanding of intra-islet GLP-1 biology may impact our understanding of the mechanisms of incretin-based therapeutics.
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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.