Pancreatic islets compose the endocrine pancreas and are considered distinct from the exocrine pancreas in terms of both function and regulation of blood flow. Indeed, enzymatically isolated islets directly respond to glucose and other secretagogues in vitro. The islet has been regarded as an enclosed micro-organ, in which blood flows uni-directionally from an afferent arteriole to an efferent venule. This blood circulation pattern has been termed as “the insulo-acinar portal system.” Historically, the endocrine and exocrine pancreas have been studied separately by different fields of investigators. Using intravital analysis of pancreas blood flow in mice, we have recently reported that islet capillaries are continuously integrated with those in the exocrine pancreas, which makes the islet circulation open, not self-contained. Furthermore, by tracking fluorescently-labeled red blood cells revealed bi-directional blood flow between the endocrine and exocrine pancreas. In the present study, in order to verify whether this integrated vascular network is conserved among different species, we carried out three-dimensional morphological analysis of pancreatic capillary networks using thick pancreatic tissue slices (600-800 µm) in ferrets, rabbits, pigs, dogs and monkeys, besides mice and humans. We have confirmed that the integrated blood flow between endocrine and exocrine pancreas is conserved among multiple species that we studied. Here we propose that the open circulation model physically links both endocrine and exocrine parts of the pancreas as a single organ through the integrated vascular network. This new paradigm may provide revived or contrasting insights into the findings of past studies, as well as a novel approach for prospective research projects.


J.K. Butterfield: None. M. Hara: None.


National Institutes of Health (DK117192, DK020595)

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