ArticleMolecular metabolism2020
Human islets contain a subpopulation of glucagon-like peptide-1 secreting α cells that is increased in type 2 diabetes.
Article in Molecular metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 78 citations in OpenAlex.
- β-cell 14-3-3-ζ and sex are key regulators of α-cell form and function.Endocrinology · 2026Article
- Pancreatic islets: new discoveries for innovative treatments of diabetes?Diabetologia · 2026Review
- Distinctive patterns of glucagon and incretin responses to oral and isoglycaemic intravenous glucose load in fibrocalculous pancreatic diabetes.Scientific reports · 2026Article
- Placenta-Derived Extracellular Vesicles (pdEVs): Key Mediators That Affect the Metabolic Health of Offspring in Early Nutritional Environments.Biomolecules · 2026Review
- Deep single-cell decoding of human pancreatic islets reveals T2D β-cell gene expression defects.The EMBO journal · 2026Article
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- SEL1L-HRD1 ER-associated degradation facilitates prohormone convertase 2 maturation and glucagon production in islet α cells.Nature communications · 2026Article
- GLP-1 physiology and pharmacology along the gut-brain axis.The Journal of clinical investigation · 2026Review
- Human pancreatic α-cell heterogeneity and trajectory inference analyses reveal SMOC1 as a β-cell dedifferentiation gene.Nature communications · 2025Article
- α cells use both PC1/3 and PC2 to process proglucagon peptides and control insulin secretion.Science advances · 2025Article
- Adipose Tissue, at the Core of the Action of Incretin and Glucagon-Based Anti-Obesity Drugs.Current obesity reports · 2025Review
- A new paradigm of islet adaptations in human pregnancy: insights from immunohistochemistry and proteomics.Nature communications · 2025Article
- Modeling diabetic alpha cell dysfunction using stem cell-derived alpha cells.Stem cell reports · 2025Article
- Article
- Single-cell decoding of human islet cell type-specific alterations in type 2 diabetes reveals converging genetic- and state-drivenbioRxiv : the preprint server for biology · 2025Article
- Quantitative analysis of islet prohormone convertase 1/3 expression in human pancreas donors with diabetes.Diabetologia · 2024Article
- Liraglutide Effect on Weight and A1C in Patients with Type 2 Diabetes Mellitus: Real-World Data from a Single Tertiary Care Center in Saudi Arabia.Journal of pharmacy & bioallied sciences · 2024Article
- 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
- Redox Status as a Key Driver of Healthy Pancreatic Beta-Cells.Physiological research · 2024Review
- Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
objectivesOur study shows that glucagon-like peptide-1 (GLP-1) is secreted within human islets and may play an unexpectedly important paracrine role in islet physiology and pathophysiology. It is known that α cells within rodent and human pancreatic islets are capable of secreting GLP-1, but little is known about the functional role that islet-derived GLP-1 plays in human islets.
methodsWe used flow cytometry, immunohistochemistry, perifusions, and calcium imaging techniques to analyse GLP-1 expression and function in islets isolated from cadaveric human donors with or without type 2 diabetes. We also used immunohistochemistry to analyse GLP-1 expression within islets from pancreatic biopsies obtained from living donors.
resultsWe have demonstrated that human islets secrete ∼50-fold more GLP-1 than murine islets and that ∼40% of the total human α cells contain GLP-1. Our results also confirm that dipeptidyl peptidase-4 (DPP4) is expressed in α cells. Sitagliptin increased GLP-1 secretion from cultured human islets but did not enhance glucose-stimulated insulin secretion (GSIS) in islets from non-diabetic (ND) or type 2 diabetic (T2D) donors, suggesting that β cell GLP-1 receptors (GLP-1R) may already be maximally activated. Therefore, we tested the effects of exendin-9, a GLP-1R antagonist. Exendin-9 was shown to reduce GSIS by 39% and 61% in ND islets and T2D islets, respectively. We also observed significantly more GLP-1+ α cells in T2D islets compared with ND islets obtained from cadaveric donors. Furthermore, GLP-1+ α cells were also identified in pancreatic islet sections obtained from living donors undergoing surgery.
conclusionsIn summary, we demonstrated that human islets secrete robust amounts of GLP-1 from an α cell subpopulation and that GLP-1R signalling may support GSIS to a greater extent in T2D islets.
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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 Socratic graph.