ArticleEBioMedicine2019
Abnormal regulation of glucagon secretion by human islet alpha cells in the absence of beta cells.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- CD98hc marks a precursor of human stem cell-derived alpha cells primed for functional maturation.Frontiers in endocrinology · 2026Article
- Scaffold-free endocrine tissue engineering: role of islet organization and implications in type 1 diabetes.BMC endocrine disorders · 2025Review
- Regulatory Role of Fatty Acid Metabolism on Glucose-Induced Changes in Insulin and Glucagon Secretion by Pancreatic Islet Cells.International journal of molecular sciences · 2024Review
- Understanding the Structural Arrangement of Islets in Chronic Pancreatitis.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2024Article
- Fluorescein-based sensors to purify human α-cells for functional and transcriptomic analyses.eLife · 2023Article
- The human α cell in health and disease.The Journal of endocrinology · 2023Review
- Small molecule glucagon release inhibitors with activity in human islets.Frontiers in endocrinology · 2023Article
- Multiplexed microfluidic platform for stem-cell derived pancreatic islet β cells.Lab on a chip · 2022Article
- Article
- Review
- Combinatorial transcription factor profiles predict mature and functional human islet α and β cells.JCI insight · 2021Article
- The Role of the α Cell in the Pathogenesis of Diabetes: A World beyond the Mirror.International journal of molecular sciences · 2021Review
- Islet sympathetic innervation and islet neuropathology in patients with type 1 diabetes.Scientific reports · 2021Article
- Current progress in stem cell therapy for type 1 diabetes mellitus.Stem cell research & therapy · 2020Review
- Approaches to Manipulate Ephrin-A:EphA Forward Signaling Pathway.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Cell Heterogeneity and Paracrine Interactions in Human Islet Function: A Perspective Focused in β-Cell Regeneration Strategies.Frontiers in endocrinology · 2020Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundThe understanding of the regulation of glucagon secretion by pancreatic islet α-cells remains elusive. We aimed to develop an in vitro model for investigating the function of human α-cells under direct influence of glucose and other potential regulators.
methodsHighly purified human α-cells from islets of deceased donors were re-aggregated in the presence or absence of β-cells in culture, evaluated for glucagon secretion under various treatment conditions, and compared to that of intact human islets and non-sorted islet cell aggregates.
findingsThe pure human α-cell aggregates maintained proper glucagon secretion capability at low concentrations of glucose, but failed to respond to changes in ambient glucose concentration. Addition of purified β-cells, but not the secreted factors from β-cells at low or high concentrations of glucose, partly restored the responsiveness of α-cells to glucose with regulated glucagon secretion. The EphA stimulator ephrinA5-fc failed to mimic the inhibitory effect of β-cells on glucagon secretion. Glibenclamide inhibited glucagon secretion from islets and the α- and β-mixed cell-aggregates, but not from the α-cell-only aggregates, at 2.0 mM glucose.
interpretationThis study validated the use of isolated and then re-aggregated human islet cells for investigating α-cell function and paracrine regulation, and demonstrated the importance of cell-to-cell contact between α- and β-cells on glucagon secretion. Loss of proper β- and α-cell physical interaction in islets likely contributes to the dysregulated glucagon secretion in diabetic patients. Re-aggregated select combinations of human islet cells provide unique platforms for studying islet cell function and regulation.
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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 OpenQuestion graph.