The DOI matches its Crossref record; 23 of the 28 references it cites were found in a registry or an index.
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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“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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“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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Cites
β-Cell Deficit and Increased β-Cell Apoptosis in Humans With Type 2 Diabetes
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“Human islet isolations were performed as previously described according to the Ricordi method with local adaptations (13,14).”
MethodThe unique cytoarchitecture of human pancreatic islets has implications for islet cell function
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“Our description of human islet cell organization is innovative but does not contradict the different views reported so far about the human islet architecture (6,8,9,11,12), including the diametrically opposed opinions describing islets with either segregated or intermingled cell types.”
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“Our description of human islet cell organization is innovative but does not contradict the different views reported so far about the human islet architecture (6,8,9,11,12), including the diametrically opposed opinions describing islets with either segregated or intermingled cell types.”
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“This last observation is in agreement with published works showing a decrease of betacell mass in type 2 diabetes (16-19).”
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“This unique architecture appears to have some functional implications (1).”
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“A physiological relevance of this unique plasticity of beta-cells is possible, especially considering that glucose-induced insulin secretion in vitro is improved in spreading beta-cells compared to roundshaped beta-cells (23) and that cytoskeleton plays a role in insulin secretion (24).”
BackgroundSelf-citationGlucagon receptors on human islet cells contribute to glucose competence of insulin release
Huypens, P., Ling, Z., PIPELEERS, D. G., & Schuit, F. C. (2000) · Diabetologia · doi:10.1007/s001250051484 · Cited by 226 · cited 1×
“showing that glucagon positively affected insulin release (20,21).”
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“In addition, in vitro experiments showed that homologous contacts between rat -cells improved their function, as heterologous contacts between - and non– -cells had no effect (3).”
BackgroundSelf-citation
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“The reason why the proportion of alpha cells increases with the size of the islet [6, 19] is not known, but this variation may complicate comparisons of data obtained in different studies if not all sections of islets are counted.”
BackgroundResultPARACRINE INTERACTIONS WITHIN THE PANCREATIC ISLET DETERMINE THE GLYCEMIC SET POINT
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“Most of the cells in the islet core stained for insulin, while the glucagon-containing cells were located peripherally in small and randomly in large islets, as previously reported [37].”
ADCY5 Couples Glucose to Insulin Secretion in Human Islets
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BackgroundOf rodents and men: Species-specific glucose regulation and type 2 diabetes research
Chandrasekera, P. C. (2014) · ALTEX · doi:10.14573/1309231 · Cited by 88
“…β-cells intermingle with all other cell types compared to the homotypic associations prominent in mouse β-cells (Brissova et al., 2005; Cabrera et al., 2006; Kim et al., 2009), other than in one study that identified some small human islets displaying mouse-like segregation (Bosco et al., 2010).”
The Pancreatic β-Cell: A Bioenergetic Perspective
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“However, Bosco et al. (2010) found that, “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.”
BackgroundResultInfluentialRisk of Diabetes Mellitus in Long-Term Survivors of Hodgkin Lymphoma
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Braun, M. (2014) · Vitamins and hormones · doi:10.1016/b978-0-12-800174-5.00007-7 · Cited by 70
“Blood vessels were found to run adjacent to the non-b-cell layers (Bosco et al., 2010).”
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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).”
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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).”
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Lefèbvre, P. J., Paquot, N., & Scheen, A. J. (2015) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12480 · Cited by 45
Metadata
- 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 › Endocrinology, Diabetes and Metabolism › 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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