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

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 ␤ cells, glucagon-immunoreactive ␣ cells, and somatostatin-containing ␦ cells were found scattered throughout the human islet. Human ␤ 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 ␤ cells and more ␣ cells than did mouse islets. In human islets, most ␤, ␣, and ␦ 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 ␤ 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 ␣ cells to the islet composition. We conclude that the unique cellular arrangement of human islets has functional implications for islet cell function.␣ cell ͉ ␤ cell ͉ cytoplasmic free Ca 2ϩ concentration ͉ insulin ͉ glucagon I n the last three decades, hundreds of individuals with type 1 diabetes mellitus have received allogeneic transplants of endocrine pancreas, the islets of Langerhans, to cure their chronic condition. In these patients, diabetes is reversed by transplanting cells capable of physiologically regulating insulin secretion. Determining the quality of islets obtained from cadaveric pancreata should be indispensable in this context. However, it is not known which physiological parameters correlate best with a fully functional islet capable of reversing diabetes after transplantation. There is a wealth of information about the physiology of rodent islets, but the biology of human islets remains poorly understood. As assays for determining islet quality are being developed by many laboratories in the field of islet transplantation, a reassessment of the structure and function of human islets is warranted.The islets of Langerhans are small organs located in the pancreas that are crucial for glucose homeostasis. Islets typically consist of four types of secretory endocrine cells, namely, the insulin-containing ␤ cells, the glucagon-containing ␣ cells, the somatostatin-containing ␦ cells, and the pancreatic polypeptideproducing (PP) cells. In rodent islets, the vastly predominating ␤ cells are clustered in the core of a generally round islet, surrounded by a mantle of ␣, ␦, and PP cells. Thus, ...

Beta-cell hubs maintain Ca2+ oscillations in human and mouse islet simulations

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Mathematical modeling and statistical analysis of calcium-regulated insulin granule exocytosis in β-cells from mice and humans

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Filtration is a time-efficient option to Histopaque, providing good-quality islets in mouse islet isolation

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