Blood Flow in the Pancreatic Islet: Not so Isolated Anymore.

Abstract

The pancreatic islet is a highly vascularized endocrine mini-organ that depends on blood supply to function efficiently. As blood flows through islet capillaries reaching different endocrine cell types, it significantly impacts nutrient sensing, paracrine communication, and the final hormonal output. Thus, any change in blood flow, either induced physiologically (e.g., nervous input) or as a result of pathological changes (e.g., fibrosis), could affect islet function. It is not a stretch to state that the way the islet vasculature is arranged anatomically and regulated functionally must have consequences for glucose homeostasis. Despite its potential impact for islet function, interest in the islet vasculature has been sporadic and is certainly not equal to that professed to the cells it serves. Still, there has been a substantive research effort in this arena. From beautiful scanning electron images of corrosion casts (1) to creative physiological experiments using perfused pancreases (2) and microbeads (3), investigators have employed various approaches to study the microcirculation of the islet. The results of these studies provided structural and functional insight but also raised questions. To settle a debate that had started in the mid-1960s, a group of prominent islet biologists decided to meet in 1996 to review existing notions about islet blood flow and “agreed to disagree” that there were three models (4). In model 1, non–β-cells are perfused before β-cells, allowing other endocrine cells to influence β-cells located downstream. In model 2, β-cells are perfused before the other endocrine cells and thus dominate islet function. In model 3, there is no apparent order of perfusion, but blood …