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

Proceedings of the National Academy of Sciences of the United States of America - Tập 103 Số 7 - Trang 2334-2339 - 2006
Over Cabrera1, Dora M. Berman2, Norma S. Kenyon2, Camillo Ricordi2, Per‐Olof Berggren2,3, Alejandro Caicedo2
1Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL 33136, USA
2*Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL 33136; and
3The Rolf Luft Center for Diabetes Research, Department of Molecular Medicine, Karolinska Institutet, SE-171 76, Stockholm, Sweden

Tóm tắt

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 Ca 2+ concentration, [Ca 2+ ] 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 [Ca 2+ ] 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.

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Thông tin xuất bản

Proceedings of the National Academy of Sciences of the United States of America

Tập 103 Số 7

2334-2339

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