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
Butler, A. E., Janson, J., Bonner-Weir, S., Ritzel, R., Rizza, R. A., & Butler, P. C. (2003) · Diabetes · doi:10.2337/diabetes.52.1.102 · Cited by 4,011
Automated Method for Isolation of Human Pancreatic Islets
Ricordi, C., Lacy, P. E., FINKE, E. H., Olack, B. J., & Scharp, D. W. (1988) · Diabetes · doi:10.2337/diab.37.4.413 · Cited by 1,321 · cited 1×
“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
Cabrera, O., Berman, D. M., Kenyon, N. S., Ricordi, C., Berggren, P.-O., & Caicedo, A. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510790103 · Cited by 1,312 · cited 2×
“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.”
BackgroundBrissova, M., Fowler, M. J., Nicholson, W. E., Chu, A., Hirshberg, B., Harlan, D. M., & Powers, A. C. (2005) · Journal of Histochemistry & Cytochemistry · doi:10.1369/jhc.5c6684.2005 · Cited by 797 · cited 2×
“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.”
BackgroundSakuraba, H., Mizukami, H., Yagihashi, N., Wada, R., Hanyu, C., & Yagihashi, S. (2002) · Diabetologia · doi:10.1007/s125-002-8248-z · Cited by 699 · cited 2×
“This last observation is in agreement with published works showing a decrease of betacell mass in type 2 diabetes (16-19).”
ResultIslet pathology and the pathogenesis of type 1 and type 2 diabetes mellitus revisited.
Klöppel, G., Löhr, M., Habich, K., Oberholzer, M., & Heitz, P. (1985) · Survey and Synthesis of Pathology Research · doi:10.1159/000156969 · Cited by 645
Functional subdivision of islets of Langerhans and possible role of D cells.
Orci, L., & Unger, R. H. (1975) · The Lancet · doi:10.1016/s0140-6736(75)92078-4 · Cited by 442 · cited 2×
“This unique architecture appears to have some functional implications (1).”
BackgroundBosco, D., Meda, P., Halban, P., & Rouiller, D. (2000) · Diabetes · doi:10.2337/diabetes.49.2.233 · Cited by 227 · cited 2×
“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).”
BackgroundBosco, D., Orci, L., & Meda, P. (1989) · Experimental Cell Research · doi:10.1016/0014-4827(89)90365-0 · Cited by 167 · cited 1×
“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
Flagged first, then by citations
5 of the 28 references couldn’t be matched to a known paper.
Research works printed but not linked: 4
- Gannon, 2000, Persistent expression of HNF6 in islet endocrine cells causes disrupted islet architecture and loss of beta cell function, Development, 127, 2883, 10.1242/dev.127.13.2883 · DOI
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- Grube, 1983, Immunohistochemistry and microanatomy of the islets of Langerhans, Biomed Res, 4, 25
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Items 301–316 of 316
Rupik, W., Kaczmarek, P., & Kowalska, M. (2025) · The European Zoological Journal · doi:10.1080/24750263.2025.2551705
“The arrangement of endocrine cells within the pancreatic islets varies across amniote species (Chandavar & Naik 2008; Bosco et al. 2010; Heller 2010; Kojima 2014) and can even differ within the same species (Steiner et al. 2010; Chandavar & Naik 2011).”
Effect of Maternal Hyperglycemia on Fetal Pancreatic Islet Development
Dias, C. P., de Moraes, M. R. T. P., Barrence, F. A. C., da Silva, C. S. B., Smuckzec, B., Ortis, F., & Zorn, T. M. T. (2025) · Biology · doi:10.3390/biology14060728
“Similar modifications have been observed in models of mild maternal diabetes and in adults with DM2 as a compensatory mechanism for hyperglycemia [36,37].”
Emerging glucagon-based therapies in diabetes mellitus: Toward a better future in diabetes care
Gnanathayalan, S., & Sumanatilleke, M. (2024) · Journal of Diabetology · doi:10.4103/jod.jod_110_23
Biochemical pancreatic β-cell lineage reprogramming: Various cell fate shifts
Wang, Y., Liu, Z., Li, S., Su, X., Lai, K. P., & Li, R. (2023) · Current Research in Translational Medicine · doi:10.1016/j.retram.2023.103412
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Saadati, M., & Jamali, Y. (2020) · Research Square · doi:10.21203/rs.3.rs-132280/v1
Ontogeny of the Human Pancreas
Proshchina, A. E., Krivova, Y. S., Gurevich, L. E., Barabanov, V. M., Otlyga, D., Voronkova, I. А., & Saveliev, S. V. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.84515
Glucagon in Islet and Metabolic Regulation
Sandoval, D. A., Tong, J., & Alessio, D. D. (2016) · Wiley eBooks · doi:10.1002/9781118924853.ch7 · Cited by 1
2.グルカゴン分泌の分子機構：Paracrine Regulation
河盛, 段., 金藤, 秀., & 伊一郎, 下. (2012) · doi:10.11213/tonyobyo.55.841
Structure and properties of insulin
Gupta, A. (2022) · Understanding Insulin and Insulin Resistance · doi:10.1016/b978-0-12-820234-0.00004-4
A demanding path from iPSCs toward pancreatic β- and α-cells
Marques, J. M., Nunes, R., Florindo, H. F., Ferreira, D., & Sarmento, B. F. C. C. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-822230-0.00002-8
Analysis and modelling of spatial organization of 3D tissues in biological images
nhu, H. T. T. (2018) · theses.fr (ABES) · doi:10.70675/133a6a87z190fz4092z91d4z09136e03378a
“(2010) [6] detects the unique association between alpha- and beta- cells in human islet cells from at least 10 different pancreas.”
InfluentialSynthetic biology technologies for beta cell generation
Saxena, P., Bojar, D., Zulewski, H., & Fussenegger, M. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-814831-0.00030-0
Piro, S., Urbano, F., Folli, F. B., Finzi, G., Marselli, L., & Marchetti, P. (2016) · Endocrinology · doi:10.1007/978-3-319-27318-1_31-1 · Cited by 1
Studies relating to the differentiation of human embryonic stem cells
Ανυφαντής, Γ. (2015) · doi:10.12681/eadd/61145
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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