The unique cytoarchitecture of human pancreatic islets has implications for islet cell function

O Cabrera, DM Berman, NS Kenyon… - Proceedings of the …, 2006 - National Acad Sciences
O Cabrera, DM Berman, NS Kenyon, C Ricordi, PO Berggren, A Caicedo
Proceedings of the National Academy of Sciences, 2006National Acad Sciences
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 …
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 α cells to the islet composition. We conclude that the unique cellular arrangement of human islets has functional implications for islet cell function.
National Acad Sciences