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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Citations
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-citationTomas, A., Yermen, B., Min, L., Pessin, J., & Halban, P. (2006) · Journal of Cell Science · doi:10.1242/jcs.02942 · Cited by 165
Saito, K., Yaginuma, N., & Takahashi, T. (1979) · Tohoku journal of experimental medicine · doi:10.1620/tjem.129.273 · Cited by 156 · cited 2×
“This last observation is in agreement with published works showing a decrease of betacell mass in type 2 diabetes (16-19).”
ResultInsulin secretion from human beta cells is heterogeneous and dependent on cell-to-cell contacts
Wojtusciszyn, A., Armanet, M., Morel, P., Berney, T., & Bosco, D. (2008) · Diabetologia · doi:10.1007/s00125-008-1103-z · Cited by 141 · cited 1×
“In this respect, we recently demonstrated that insulin secretion from individual beta-cells was increased when they were in contact with alpha-cells (22).”
BackgroundSelf-citationAssessment of a Novel Two-Component Enzyme Preparation for Human Islet Isolation and Transplantation
Bucher, P., Mathe, Z., Morel, P., Bosco, D., Andres, A., Kurfuest, M., Friedrich, O., Raemsch-Guenther, N., Buhler, L., & Berney, T. (2005) · Transplantation · doi:10.1097/01.tp.0000147344.73915.c8 · Cited by 128 · cited 1×
“Human islet isolations were performed as previously described according to the Ricordi method with local adaptations (13,14).”
MethodSelf-citationEffect of glucagon on serum insulin, plasma glucose and free fatty acids in man.
Crockford, P., Porte, D., Wood, F. C., & Williams, R. H. (1966) · Metabolism: Clinical and Experimental · doi:10.1016/0026-0495(66)90032-1 · Cited by 124 · cited 1×
“showing that glucagon positively affected insulin release (20,21).”
BackgroundRouiller, D., Cirulli, V., & Halban, P. (1991) · Developmental Biology · doi:10.1016/0012-1606(91)90332-w · Cited by 98
The microanatomy of the islets of Langerhans.
Orci, L. (1976) · Metabolism: Clinical and Experimental · doi:10.1016/s0026-0495(76)80129-1 · Cited by 84 · cited 3×
“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.”
BackgroundSamols, E., & Stagner, J. I. (1988) · The American Journal of Medicine · doi:10.1016/0002-9343(88)90395-6 · Cited by 79 · cited 1×
“The characteristic islet architecture may also serve to facilitate interactions among the different islet hormones via interstitial or vascular routes (4,5).”
BackgroundBosco, D., Rouiller, D., & Halban, P. (2007) · Journal of Endocrinology · doi:10.1677/joe-06-0169 · Cited by 77 · cited 1×
“Among these components, there are the insulin secretagogues, such as glucose, that have been shown to affect expression of adhesion molecules, including E-cadherin and integrins, in islet cells (23,25).”
BackgroundSelf-citationIslets in type 2 diabetes: in honor of Dr. Robert C. Turner
Bonner-Weir, S., & O'Brien, T. D. (2008) · Diabetes · doi:10.2337/db07-1842 · Cited by 66 · 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.”
BackgroundIslet somatostatin-microvascular, paracrine, and pulsatile regulation
Samols, E., & Stagner, J. I. (1990) · Metabolism · doi:10.1016/0026-0495(90)90212-u · Cited by 58 · cited 1×
“The characteristic islet architecture may also serve to facilitate interactions among the different islet hormones via interstitial or vascular routes (4,5).”
BackgroundBosco, D., Meda, P., Morel, P., Matthey-Doret, D., Caille, D., Toso, C., Bühler, L., & Berney, T. (2005) · Diabetologia · doi:10.1007/s00125-005-1816-1 · Cited by 43 · cited 1×
“between rodent and human islets, and on the proportion of islet beta-cells that is lower in humans compared to rodents (6-8).”
BackgroundSelf-citationTumor necrosis factor-alpha modifies adhesion properties of rat islet B cells.
Cirulli, V., Halban, P., & Rouiller, D. G. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116403 · Cited by 32 · cited 1×
“This indicates that in rodents, information that decides the islet architecture is foremost provided by islet cells themselves (26,27).”
Background
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
- Erlandsen, 1976, Pancreatic islet cell hormones distribution of cell types in the islet and evidence for the presence of somatostatin and gastrin within the D cell, J Histochem Cytochem, 24, 883, 10.1177/24.7.60437 · DOI
- Grube, 1983, Immunohistochemistry and microanatomy of the islets of Langerhans, Biomed Res, 4, 25
- Cunningham, 1968, Further improvements in the plaque technique for detecting single antibody-forming cells, Immunology, 14, 599
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The Discovery and Development of Liraglutide and Semaglutide
Knudsen, L. B., & Lau, J. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00155 · Cited by 970
Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men
Rorsman, P., & Ashcroft, F. M. (2018) · Physiological Reviews · doi:10.1152/physrev.00008.2017 · Cited by 793
Glucagonocentric restructuring of diabetes: A pathophysiologic and therapeutic makeover
Unger, R. H., & Cherrington, A. D. (2012) · Journal of Clinical Investigation · doi:10.1172/jci60016 · Cited by 670
Regulation of Insulin Secretion in Human Pancreatic Islets
Rorsman, P., & Braun, M. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-030212-183754 · Cited by 599
Physiology of Proglucagon Peptides: Role of Glucagon and GLP-1 in Health and Disease
Sandoval, D. A., & D'Alessio, D. A. (2015) · Physiological Reviews · doi:10.1152/physrev.00013.2014 · Cited by 498
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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