Abstract
The cytoarchitecture of human islets has been examined, focusing on cellular associations that provide the anatomical framework for paracrine interactions. By using confocal microscopy and multiple immunofluorescence, we found that, contrary to descriptions of prototypical islets in textbooks and in the literature, human islets did not show anatomical subdivisions. Insulin-immunoreactive β cells, glucagon-immunoreactive α cells, and somatostatin-containing δ cells were found scattered throughout the human islet. Human β cells were not clustered, and most (71%) showed associations with other endocrine cells, suggesting unique paracrine interactions in human islets. Human islets contained proportionally fewer β cells and more α cells than did mouse islets. In human islets, most β, α, and δ cells were aligned along blood vessels with no particular order or arrangement, indicating that islet microcirculation likely does not determine the order of paracrine interactions. We further investigated whether the unique human islet cytoarchitecture had functional implications. Applying imaging of cytoplasmic free Ca2+ concentration, [Ca2+]i, we found that β cell oscillatory activity was not coordinated throughout the human islet as it was in mouse islets. Furthermore, human islets responded with an increase in [Ca2+]i when lowering the glucose concentration to 1 mM, which can be attributed to the large contribution of a cells to the islet composition. We conclude that the unique cellular arrangement of human islets has functional implications for islet cell function.
| Original language | English |
|---|---|
| Pages (from-to) | 2334-2339 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 103 |
| Issue number | 7 |
| DOIs | |
| State | Published - Feb 14 2006 |
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Keywords
- α cell
- β cell
- Cytoplasmic free Ca concentration
- Glucagon
- Insulin
ASJC Scopus subject areas
- Genetics
- General
Cite this
The unique cytoarchitecture of human pancreatic islets has implications for islet cell function. / Cabrera, Over; Berman-Weinberg, Dora; Kenyon, Norma S; Ricordi, Camillo; Berggren, Per Olof; Caicedo-Vierkant, Diego A.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 7, 14.02.2006, p. 2334-2339.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The unique cytoarchitecture of human pancreatic islets has implications for islet cell function
AU - Cabrera, Over
AU - Berman-Weinberg, Dora
AU - Kenyon, Norma S
AU - Ricordi, Camillo
AU - Berggren, Per Olof
AU - Caicedo-Vierkant, Diego A
PY - 2006/2/14
Y1 - 2006/2/14
N2 - The cytoarchitecture of human islets has been examined, focusing on cellular associations that provide the anatomical framework for paracrine interactions. By using confocal microscopy and multiple immunofluorescence, we found that, contrary to descriptions of prototypical islets in textbooks and in the literature, human islets did not show anatomical subdivisions. Insulin-immunoreactive β cells, glucagon-immunoreactive α cells, and somatostatin-containing δ cells were found scattered throughout the human islet. Human β cells were not clustered, and most (71%) showed associations with other endocrine cells, suggesting unique paracrine interactions in human islets. Human islets contained proportionally fewer β cells and more α cells than did mouse islets. In human islets, most β, α, and δ cells were aligned along blood vessels with no particular order or arrangement, indicating that islet microcirculation likely does not determine the order of paracrine interactions. We further investigated whether the unique human islet cytoarchitecture had functional implications. Applying imaging of cytoplasmic free Ca2+ concentration, [Ca2+]i, we found that β cell oscillatory activity was not coordinated throughout the human islet as it was in mouse islets. Furthermore, human islets responded with an increase in [Ca2+]i when lowering the glucose concentration to 1 mM, which can be attributed to the large contribution of a cells to the islet composition. We conclude that the unique cellular arrangement of human islets has functional implications for islet cell function.
AB - The cytoarchitecture of human islets has been examined, focusing on cellular associations that provide the anatomical framework for paracrine interactions. By using confocal microscopy and multiple immunofluorescence, we found that, contrary to descriptions of prototypical islets in textbooks and in the literature, human islets did not show anatomical subdivisions. Insulin-immunoreactive β cells, glucagon-immunoreactive α cells, and somatostatin-containing δ cells were found scattered throughout the human islet. Human β cells were not clustered, and most (71%) showed associations with other endocrine cells, suggesting unique paracrine interactions in human islets. Human islets contained proportionally fewer β cells and more α cells than did mouse islets. In human islets, most β, α, and δ cells were aligned along blood vessels with no particular order or arrangement, indicating that islet microcirculation likely does not determine the order of paracrine interactions. We further investigated whether the unique human islet cytoarchitecture had functional implications. Applying imaging of cytoplasmic free Ca2+ concentration, [Ca2+]i, we found that β cell oscillatory activity was not coordinated throughout the human islet as it was in mouse islets. Furthermore, human islets responded with an increase in [Ca2+]i when lowering the glucose concentration to 1 mM, which can be attributed to the large contribution of a cells to the islet composition. We conclude that the unique cellular arrangement of human islets has functional implications for islet cell function.
KW - α cell
KW - β cell
KW - Cytoplasmic free Ca concentration
KW - Glucagon
KW - Insulin
UR - http://www.scopus.com/inward/record.url?scp=33144467088&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33144467088&partnerID=8YFLogxK
U2 - 10.1073/pnas.0510790103
DO - 10.1073/pnas.0510790103
M3 - Article
C2 - 16461897
AN - SCOPUS:33144467088
VL - 103
SP - 2334
EP - 2339
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 7
ER -