Unique Arrangement of α- and β-Cells in Human Islets of Langerhans
Open accessAbstract
OBJECTIVE: It is generally admitted that the endocrine cell organization in human islets is different from that of rodent islets. However, a clear description of human islet architecture has not yet been reported. The aim of this work was to describe our observations on the arrangement of human islet cells. RESEARCH DESIGN AND METHODS: Human pancreas specimens and isolated islets were processed for histology. Sections were analyzed by fluorescence microscopy after immunostaining for islet hormones and endothelial cells. RESULTS: In small human islets (40–60 μm in diameter), β-cells had a core position, α-cells had a mantle position, and vessels laid at their periphery. In bigger islets, α-cells had a similar mantle position but were found also along vessels that penetrate and branch inside the islets. As a consequence of this organization, the ratio of β-cells to α-cells was constantly higher in the core than in the mantle part of the islets, and decreased with increasing islet diameter. This core-mantle segregation of islet cells was also observed in type 2 diabetic donors but not in cultured isolated islets. Three-dimensional analysis revealed that islet cells were in fact organized into trilaminar epithelial plates, folded with different degrees of complexity and bordered by vessels on both sides. In epithelial plates, most β-cells were located in a central position but frequently showed cytoplasmic extensions between outlying non–β-cells. CONCLUSIONS: Human islets have a unique architecture allowing all endocrine cells to be adjacent to blood vessels and favoring heterologous contacts between β- and α-cells, while permitting homologous contacts between β-cells.
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Mouse islets contain a central core of electrically coupled β-cells that functions as a syncytium, whereas human islets have β-cells organized into several subdomains, with β-cells in one domain electrically insulated from β-cells in other domains by strands of non-beta-cells.
“Whereas mouse islets contain a central core of electrically coupled β-cells that functions as a syncytium, β-cells in human islets are organized into several subdomains, with β-cells in one domain being electrically insulated from β-cells in other domains by strands of non-beta-cells (82, 102).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [82]
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Experimental — accuracy not yet measuredMouse islets consist of a core of β-cells surrounded by a mantle of non-β-cells, whereas human islets have β-cells directly juxtaposed to non-β-cells and non-β-cells within the islet core.
“Mouse islets consist of a clearly demarcated core of β-cells surrounded by a mantle of non-β-cells. In contrast, human islets have a more complex architecture in which β-cells are directly juxtaposed to non-β-cells, and non-β-cells are also found within the islet core (82).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [82]
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Why does the immune system destroy pancreatic β-cells but not α-cells in type 1 diabetes?
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GLP-1 Effects on Islets: Hormonal, Neuronal, or Paracrine?
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The role of α-cells in islet function and glucose homeostasis in health and type 2 diabetes.
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“Islet architecture plays an important role in the governance of islet physiology and endocrinology, and variant morphologies can be observed concurrent with diabetic phenotypes and hyperglycemia (Bosco et al., 2010; Cabrera et al., 2006; Kilimnik et al., 2011; Kim et al., 2009).”
BackgroundThe role of the islet niche on beta cell structure and function.
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Small human islets comprised of more β-cells with higher insulin content than large islets
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“Little was done to elucidate the islet populations until the architectural variations based on size were published in 2010.(9) At about the same time, we documented several differences between the large and small rat islets that could partially explain why isolated small islets secreted more insulin per volume.”
BackgroundMethodInfluentialAll mixed up: defining roles for β-cell subtypes in mature isletsPreprint
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Tissue Engineering Approaches to Cell-Based Type 1 Diabetes Therapy
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Transcriptional control of mammalian pancreas organogenesis
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Low insulin content of large islet population is present in situ and in isolated islets
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Beta cell connectivity in pancreatic islets: a type 2 diabetes target?
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A Conserved Rule for Pancreatic Islet Organization
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Optimizing beta cell function through mesenchymal stromal cell‐mediated mitochondria transfer
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The somatostatin receptor in human pancreatic β-cells.
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“Blood vessels were found to run adjacent to the non-b-cell layers (Bosco et al., 2010).”
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Regulation of glucagon secretion by zinc: lessons from the β cell‐specific Znt8 knockout mouse model
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Pancreatic β-cell heterogeneity in health and diabetes: classes, sources, and subtypes.
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The Use of Biomaterials in Islet Transplantation
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Beta-cell hubs maintain Ca2+ oscillations in human and mouse islet simulations
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Molecular imaging of β-cells: diabetes and beyond
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Heterogeneity of human pancreatic β-cells
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The role of beta cell heterogeneity in islet function and insulin release
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“Human and rodent islets differ substantially in architecture, cell composition, proliferative capacity, islet amyloid formation, antioxidant enzyme levels, and, most significantly for the results described herein, MAFA and MAFB transcription factor expression (Bosco et al., 2010; Brissova et al., 2005; Butler et al.,…”
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The Local Paracrine Actions of the Pancreatic α-Cell
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“In in vitro perifusion studies of hormone secretion, we found that the glucagon receptor antagonists L-168,49 and des-His1-[Glu9]-glucagon (1-29) amide decreased insulin secretion stimulated by increases in glucose concentration (see also 29).”
BackgroundA roadmap of the generation of neoantigens as targets of the immune system in type 1 diabetes
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Distinct Roles of β-Cell Mass and Function During Type 1 Diabetes Onset and Remission
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“This corresponds to the reported increased frequency of and described the location of a-cells in human islets (29).”
BackgroundTargeting pancreatic β cells for diabetes treatment
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Pancreatic inflammation and increased islet macrophages in insulin-resistant juvenile primates
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Glucagon, a key factor in the pathophysiology of type 2 diabetes.
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Adult Pancreatic Alpha-Cells: A New Source of Cells for Beta-Cell Regeneration
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“Also, alpha-cells surrounded by beta-cell extensions, are often observed [49].”
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Prion-Like Protein Aggregates and Type 2 DiabetesPreprint
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“It is also important to consider that the architecture of the islets, including b-cell arrangement by the capillaries and the extent of innervation, can be significantly different in different species (Bosco et al. 2010; Rodriguez-Diaz et al. 2011).”
BackgroundInhibiting or antagonizing glucagon: making progress in diabetes care
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- Authors
- Bosco, D., Armanet, M., Morel, P., Niclauss, N., Sgroi, A., Muller, Y. D., Giovannoni, L., Parnaud, G., & Berney, T.
- Affiliations
- University of Geneva (CH)
- From the Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
- Corresponding author
- Bosco, Domenico
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2010-05-01
- Volume
- 59
- Issue
- 5
- Pages
- 1202-1210
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC2857900
- OpenAlex
- W2127238864
- Cited by
- 450
- References
- 28
- Citations by year
- 2026: 17 · 2025: 19 · 2024: 18 · 2023: 22 · 2022: 21 · 2021: 27 · 2020: 24 · 2019: 40 · 2018: 35 · 2017: 32 · 2016: 28 · 2015: 36 · 2014: 35 · 2013: 29 · 2012: 32
- FWCI
- 32.10
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (120376)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- islet architecture, alpha cells, pancreatic beta cells, core-mantle segregation, type 2 diabetes, isolated islets
- MeSH terms
- Adolescent, Adult, Aged, Cells, Cultured, Humans, Islets of Langerhans, Microscopy, Fluorescence, Middle Aged, Glucagon-Secreting Cells, Insulin-Secreting Cells, Young Adult, In Vitro Techniques
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