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

Over Cabrera, Dora M. Berman, Norma S. Kenyon, Camillo Ricordi, Per-Olof Ynge Berggren, Aiejandro Caicedo

Research output: Contribution to journalArticle

701 Scopus citations

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 languageEnglish (US)
Pages (from-to)2334-2339
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number7
DOIs
StatePublished - Feb 14 2006

Keywords

  • α cell
  • β cell
  • Cytoplasmic free Ca concentration
  • Glucagon
  • Insulin

ASJC Scopus subject areas

  • Genetics
  • General

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