Differences between studying an islet β cell and studying whole pancreatic islets: immunological implications

Abstract

The main role of the pancreatic islet β cell is to release the appropriate amount of insulin upon glucose stimulation. For this reason, islet transplantation has been advancing in the past few years as a therapeutic alternative for patients with diabetes, alongside the exciting field of manipulating β cell differentiation for the sake of β cell transplantation. However, do isolated β cells function the same as β cells within an intact islet? Within islets, β cells are surrounded by other cell types, including endocrine cells, endothelial cells and immune cells, a proximity which appears to be relevant for proper glucose homeostasis. Although insulin and glucose are the main regulators in this scenario, other factors, such as angiogenesis, local anti-inflammatory components and the activity profile of resident macrophages, have a profound effect on the function and fate of β cells. A paracrine interaction between β cells and α cell holds a dramatic effect on β cell function, which is additionally dependent on blood flow through the islet. Another important intercellular communication exists between β cells and endothelial cells, in this case a bidirectional interface. Moreover, β cell survival and proliferation is dependent on the potency of ECM proteins. Further parameters distinguish functionally between the isolated β cell and the intact islet, including the deposition of Zinc by β cells, synchronicity by electrical and calcium routes, the physical innervation of islets and more. In this review, we explore major parameters that relate to differences between the function of the isolated β cell and that of the β cell within an intact islet. These and some yet to be investigated aspects of β cell function should be included in the list of considerations when examining therapeutic targets for β cell–related pathologies and for the prospect of effective β cell replacement therapy