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 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).”
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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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5 of the 28 references couldn’t be matched to a known paper.
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Items 201–300 of 316
Exploring pancreatic pathology in Plasmodium falciparum malaria patients
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“The pattern of endocrine cell arrangement in the pancreatic islets varies among amniotes (Bosco et al., 2010; Chanda- var & Naik, 2008; Heller, 2010; Kojima, 2014) and even within species (Chandavar & Naik, 2011; Steiner, Kim, Miller, & Hara, 2010).”
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State of the Art of Bioengineering Approaches in Beta-Cell Replacement
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MDIC3: Matrix decomposition to infer cell-cell communication
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Sionov, R. V., & Ahdut-HaCohen, R. (2023) · Biomedicines · doi:10.3390/biomedicines11092558 · Cited by 13
“In contrast, the larger islets are supplied by up to three arterioles [66,70,71].”
BackgroundMultiplexed microfluidic platform for stem-cell derived pancreatic islet β cells
Goswami, I., de Klerk, E., Carnese, P., Hebrok, M., & Healy, K. (2022) · bioRxiv · doi:10.1101/2022.05.23.493153 · Cited by 8
Comparative analysis of reconstructed architectures from mice and human islets
Félix‐Martínez, G. J., & Godínez-Fernández, J. R. (2021) · Islets · doi:10.1080/19382014.2021.1987827 · Cited by 18
The Potential of Pancreatic Organoids for Diabetes Research and Therapy
Bittenglová, K., Habart, D., Saudek, F., & Koblas, T. (2021) · Islets · doi:10.1080/19382014.2021.1941555 · Cited by 16
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Self-citationA new perspective of probe development for imaging pancreatic beta cell in vivo.
Neo, C. W. Y., Ciaramicoli, L. M., Soetedjo, A. A. P., Teo, A., & Kang, N.-Y. (2020) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2020.01.009 · Cited by 8
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“Factors such as polyclonal β -cell origins, heterogeneous expression of channels and transporters, and the presence of non-β -cells creating ‘‘bottlenecks’’ (4,84–87) likely underlie the ‘‘islets within islets’’ phenomenon.”
Yang, L., Yu, X.-X., Wang, X., Jin, C.-T., & Xu, C.-R. (2025) · Science Advances · doi:10.1126/sciadv.adt4770 · Cited by 7
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“While substantial anatomical diversity exists between human islets within a single pancreas, sub-islet anatomical clusters occur, each possessing a core of beta-cells surrounded by alpha-and delta-cells [38].”
Pleiotrophin Expression and Actions in Pancreatic β-Cells
Sevillano, J., Liang, A.-M., Strutt, B., Hill, T., Szlapinski, S. K., Ramos-Álvarez, M., & Hill, D. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.777868 · Cited by 7
“larger islets in humans (25), although the percentage of islet cells represented by b-cells overall is lower than in mouse islets.”
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β‐Cell mass and function in human type 2 diabetes
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“One key reason that this debate is still unresolved is that relatively few human pancreatic micrographs have been examined quantitatively, in detail [8], to decide the cellular architecture.”
InfluentialHahm, J., Thirunavukarasu, B., Gadoo, R., Andrade, J. A. F., Dalton, T., Arany, E. J., & Hill, D. J. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252011152 · Cited by 8
“For each IPGTT curve, an area under the curve (AUC) was calculated with the exclusion of the area below the initial fasting blood glucose level to quantify the displacement of blood glucose from the fasting level [72].”
MethodTipping-point transition from transient to persistent inflammation in pancreatic islets
Holst‐Hansen, T., Yde, P., Jensen, M. H., Mandrup-Poulsen, T. R., & Trusina, A. (2024) · npj Systems Biology and Applications · doi:10.1038/s41540-024-00427-4 · Cited by 6
“…present a unique model system for quantitativeunderstanding, asisletgeometryandtheircellularcomposition are well described across many species 18 – 20 , the IL-1 β regulatory network is wellstudied,andisletscompriseacomputationallyamenablenumberofIL-1 β secreting cells, (ISC, β -cells or…”
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“Endocrine islets are embedded in exocrine pancreas tissue, which produces and delivers digestive enzymes to the intestinal tract (Bosco et al., 2010; Tiso et al., 2009).”
BackgroundInfluentialCilia Action in Islets: Lessons From Mouse Models
Cho, J. H., & Hughes, J. W. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.922983 · Cited by 7
L’îlot pancréatique : ce que nous savons 150 ans après Langerhans
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Ketosis-Prone Atypical Diabetes: Glucagon Is There, Too
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Physiological and Pathophysiological Control of Glucagon Secretion by Pancreatic α-Cells
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Diabetes as a Paracrinopathy of the Islets of Langerhans
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“These differences probably relate to differences in mouse and human islet architectures: mouse islets have a large, highly connected β-cell core, whereas human islets are composed of distinct clusters of gap junction coupled β-cells [67, 100, 101].”
BackgroundTripartite cell networks for glucose homeostasis
Song, T., & Jo, J. (2019) · Physical Biology · doi:10.1088/1478-3975/ab2a9d · Cited by 6
Regulation of the Distribution of Cells in Mixed Spheroids by Altering Migration Direction
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“Several studies described a-, b-, d-, and PP-cell populations in isolated islets of mammals, including humans, monkeys, mice, and pigs [5,6,29], However, the isolated caprine islets have been scarcely explored.”
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Generating Pancreatic Endocrine Cells from Pluripotent Stem Cells
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Modeling the Amino Acid Effect on Glucagon Secretion from Pancreatic Alpha Cells
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“Pancreatic alpha cells are found both at the mantle and the core of the islets of Langerhans and make up ~35–40% of the human islet cells [4,6].”
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Glucagon’s Golden Jubilee at the University of Liège
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Wavelength-Dependent Calcium Signaling Response to Photobiomodulation in Pancreatic Cells
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Ion Channels and Regulation of Insulin Secretion in Beta-Cells
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“In contrast, human islets exhibit a more intricate architecture, with both non-beta cells and beta cells present in the core, often in close proximity [17].”
Toren, E., Liu, Y., Bethea, M. M., Wade, A. K., & Hunter, C. S. (2022) · The FASEB Journal · doi:10.1096/fj.202200410r · Cited by 7
Cell Networks in Endocrine/Neuroendocrine Gland Function
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“Assessment of islet development has shown that human islets are in fact similar to rodent islets during embryogenesis; however, there is a tertiary folding step that leads to a concertina effect and the apparent random alpha-cell - beta-cell arrangement (46).”
PET probes for imaging pancreatic islet cells
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Thérapie cellulaire du diabète de type 1 : un pancréas bio-artificiel, sinon rien ?
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Islet Cell Therapy and Pancreatic Stem Cells
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Le rôle du glucagon dans la physiopathologie du diabète
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“…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., 2007; Cabrera et al., 2006; Dai et al., 2012; Fiaschi-Taesch et al., 2010; Henquin et al.,…”
Geometric and topological characterization of the cytoarchitecture of islets of Langerhans
Aggarwal, M., Striegel, D. A., Hara, M., & Periwal, V. (2023) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1011617 · Cited by 3
“For example, [7] observed that small human islets (40–60 μ m in diameter) in their study had β -cells in a core position, α -cells in a mantle position, and vessels at the periphery.”
BackgroundInfluentialCao, S., Wang, L., Feng, Y., Peng, X.-D., & Li, L. M. (2023) · PLoS ONE · doi:10.1371/journal.pone.0292579 · Cited by 2
Solehah, P. O., Tarusu, F. A., Tandi, J., Dewi, N. P., Lintin, G. B. R., Fitriana, Y., & Pakaya, D. (2019) · Jurnal Farmasi Galenika (Galenika Journal of Pharmacy) · doi:10.22487/j24428744.0.v0.i0.13934 · Cited by 2
“Sedangkan, dimungkinkan alkaloid berperan dalam regenerasi sel, dengan memulihkan sel β pankreas yang mengalami kerusakan parsial (Gupta & Neera, 2006; Awika & Duodu., 2016; Jayathilake et al., 2018) sehingga terjadi perbaikan morfometri pankreas.”
BackgroundDiabetes - Damages and Treatments
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Molecular Mechanism Underlying the Intra-Islet Regulation of Glucagon Secretion
Kawamori, D., & Rohit, N. K. (2011) · InTech eBooks · doi:10.5772/24792 · Cited by 1
Anatomy and Embryology of the Pancreatic Gland
Urbas, R., Klieser, E., Neureiter, D., & Brenner, E. (2021) · doi:10.1007/978-3-030-53786-9_11 · Cited by 2
Plasma scaffolds for islet transplantation
Maillard, É. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-814831-0.00018-x · Cited by 4
Anatomy, Histology, and Function of the Pancreas
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Crinophagy in Pancreatic Beta Cells: From Insulin Granule Turnover to Diabetes Pathogenesis
Mani, M., & Martin, T. F. J. (2026) · Pathophysiology · doi:10.3390/pathophysiology33030045 · Cited by 1
“…synchronized activity supported by gap-junction coupling and polarized organization around capillaries, whereas human islets contain a lower proportion of β -cells, greater α -cell abundance, and more heterogeneous cellular arrangements that vary across individuals and pancreatic regions [7,8].”
Pancreatic tissue engineering: towards a vascularized bioengineered cure for diabetes
Park, J., Olawuyi, K., Jikaria, N. R., Dawes, J. S., Dabsha, I. E., Dick, A. A., & Ravnic, D. J. (2026) · Frontiers in Transplantation · doi:10.3389/frtra.2026.1768497 · Cited by 1
“Glucose homeostasis is governed by a multicellular endocrine network composed of β -, alpha ( α )-, delta ( δ )-, and pancreatic polypeptide (PP) cells embedded within a richly vascularized microenvironment that enables rapid nutrient sensing and hormone exchange (8, 9).”
Adenosine as a modulator of human islet function and hypoxic tolerance
Perrier, Q., Jones, A., Sganga, T., Byers, L. N., Ritchey, T., Lablanche, S., Fraker, C. A., Fisher-Wellman, K. H., Tomei, A. A., Bottino, R., et al. (2026) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2026.1828405 · Cited by 1
“However, the profound architectural, cellular, and physiological differences between rodent and human islets (HI), including distinct cellular compositions and paracrine regulatory networks preclude the direct extrapolation of these findings (Bosco et al., 2010; Cottet-Dumoulin et al., 2023).”
Barsukova, A. D., Weng, L., Szymanska-Vandendriessche, K. J., Scott, M., Langer, R., & Traverso, G. (2026) · Journal of Controlled Release · doi:10.1016/j.jconrel.2026.114914 · Cited by 1
Bridging the Gap Between Static Histology and Dynamic Organ-on-a-Chip Models
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“Anatomical studies have shown that human pancreatic islets exhibit a patterned yet somewhat random distribution of α -cells and β -cells, whereas cells cultured directly in vitro display no such organization [194].”
Yabe, S., Nishida, J., Fukuda, S., Kin, T., Nishiyama, A., Tamura, T., Takeda, F., Tamura-Nakano, M., Shirakawa, J., & Okochi, H. (2025) · Gene · doi:10.1016/j.gene.2025.149639 · Cited by 1
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“Bosco et al. revealed that this cellular distribution is unique to the large human islets and, the smaller islets had similar core-mantle distribution as in the rodent islets, yet in cultured human islets, central localization of the beta-cells increases [62].”
Semaglutide and obesity: beyond the nutritional and lifestyle intervention?
Basile, L., Cannarella, R., Iuliano, S., Calogero, A. E., Condorelli, R. A., Greco, E. A., Aversa, A., & Vignera, S. L. (2024) · Minerva Endocrinology · doi:10.23736/s2724-6507.23.04103-9 · Cited by 10
In Vitro Human Fetal Pancreatic Islets to Redefine Pancreatic Research
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Pancreatic islet regeneration: Therapeutic potential, unknowns and controversy
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Pancreatic morphology in normal and diabetic states
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Mathematical Modeling of Islet Generation, Degeneration and Regeneration
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Islet Cell Therapy and Pancreatic Stem Cells
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4. New Insights of Islet Biology and the Pathophysiology of Type 2 Diabetes
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Citologija in histologija človeka
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The emerging role of epsilon cells in glucose homeostasis and lipostasis
Pavithra, N., Singh, S. A., Begum, R. F., Undela, K., Nirenjen, S., Keerthana, B., Singh, A., Mageswari, R., & Sabarathinam, S. (2025) · Obesity Medicine · doi:10.1016/j.obmed.2025.100672
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“The devices were designed in two configurations: one with a single chamber and another with two chambers, reflecting the trilaminar model of Bosco et al. [9].”
Influential
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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