Abstract
The pancreas is regarded as consisting of two separate organ systems, the endocrine and exocrine pancreas. While treatment of a disease with either an endocrine or exocrine pathogenesis may affect the function of the entire pancreas, the pancreatic diseases have been treated by clinicians in different medical disciplines, including endocrinologists and gastroenterologists. Islet microcirculation has long been considered to be regulated independently from that of the exocrine pancreas. A new model proposes that pancreatic islet blood flow is integrated with the surrounding exocrine capillary network. This recent model may provide revived or contrasting hypotheses to test, since the pancreatic microcirculation has critical implications for the regulation of islet hormones as well as acinar pancreas functions. In this mini-review, practical applications of in vivo and in situ studies of islet microcirculation are described with a specific emphasis on large-scale data analysis to ensure sufficient sample size accounting for known islet heterogeneity. For in vivo small animal studies, intravital microscopy based on two-photon excitation microscopes is a powerful tool that enables capturing the flow direction and speed of individual fluorescent-labeled red blood cells. Complementarily, for structural analysis of blood vessels, the recent technical advancements of confocal microscopy and tissue clearing have enabled us to image the three-dimensional network structure in thick tissue slices.
Highlights
In 1869, Paul Langerhans as a medical student first described the islet cells from rabbit pancreas as “small irregularly polygonal structures” that “gathered in rounded masses, 0.12-0.24 mm in diameter, distributed at regular intervals in the parenchyma”
The three previously discussed models of islet microcirculation, in which blood flows from non-beta-cells to beta-cells, beta-cells to non-beta-cells, or unidirectional via a gated portal system, were developed using distinct experimental methods [15]
Analysis of corrosion casts allowed for fine observation of microvascular details but failed to account for directionality of individual vessels, possibly contributing to the development of the insulo-acinar portal system hypothesis, in which efferent blood from the islets drains to the surrounding exocrine tissue
Summary
In 1869, Paul Langerhans as a medical student first described the islet cells from rabbit pancreas as “small irregularly polygonal structures” that “gathered in rounded masses, 0.12-0.24 mm in diameter, distributed at regular intervals in the parenchyma”. 3D immunohistochemical microscopy has permitted visualization of the islet in its entire microenvironment and has provided new insight into islet architecture, such as the lack of a mantle consisting of non-beta-cells in rodent islets when observed in 3D [12]. Such 3D techniques involve imaging of ~600-800mm thick slices of pancreatic tissue, whereas traditional 2D techniques use sections ~5μm thick, making the former more reasonable to visualize whole islets simultaneously since the vast majority of islets tend to be less than 200μm in diameter [13]. As such technological advances continue to change, though, precautions should be taken to understand potential limitations of contemporary techniques when interpreting experimental results
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