Histochemical Insights into Pancreatic Islet Biology.

The present issue of the Journal of Histochemistry and Cytochemistry is a collection of articles on the theme of “Histochemical Insights into Pancreatic Islet Biology”. This year, 2015, marks the 60th anniversary of the publication of a paper describing what can be considered to be the first true histochemical approach to staining islet β cells (Barrnett et al. 1955). These investigators applied histochemical techniques that they had developed for detecting sulfhydryl and disulfide groups of proteins specifically to the task of staining β cells and demonstrating the validity of this approach in pathophysiological experiments. 2015 also marks 63 years of publication of the Journal of Histochemistry and Cytochemistry. Over its history, the journal has published many articles on pancreatic islet cells, including an analysis of the chemistry of Gomori’s aldehyde fuchsin stain for islet β cells in the first volume of the journal (Scott and Clayton 1953). Indeed, research in the fields of metabolism and diabetes have benefitted immensely from the contributions of histochemical techniques to the study of pancreatic islet biology, both in humans and experimental animal models. Significantly, advances in techniques for detecting and imaging islet cells have led to new knowledge of the development, morphology, physiology, and pathology of islets and their roles in glucose homeostasis and diabetes. The present issue of the journal celebrates this rich history with a collection of articles that focus on the field of islet biology. The introductory perspective article (Baskin 2015) chronicles the development of key staining and histochemical techniques that have been used to identify islet cell types over the years. This account is followed by three reviews, each focused on a topic of current interest among islet investigators. Marty-Santos and Cleaver (2015) highlight an understudied area in pancreas development, namely the earliest stages of pancreas morphogenesis and the emergence of islet cell and other pancreatic lineages from a common embryonic progenitor epithelium. The review covers in detail the key events that lead eventually to differentiation of the endocrine compartment, acini and pancreatic ducts, as well as the impact of the mesenchymal extracellular matrix in the development of the pancreas three-dimensional architecture. Brereton et al. (2015) review the status of our understanding of islet cellular architecture, with an emphasis on the roles of non-β endocrine cells in facilitating intercellular communication and thereby contributing to glucose homeostasis. The article also discusses the emerging concept of islet cell plasticity, reviewing recent evidence that suggests adult islet cells may have the capability of changing their hormone-expressing profile. Hull et al. (2015) review the role of the extracellular matrix component hyaluronan in islet pathology in type 1 diabetes and in the formation of islet amyloid, a well-known component of islet pathology in type 2 diabetes. The article covers research indicating that hyaluronan accumulation in the islet contributes to an inflammatory milieu that could play a critical role in β-cell dysfunction and death in both type 1 and type 2 diabetes. The issue features six original research articles, starting with Bonner-Weir et al. (2015), who address controversial issues about the architecture of human islets and rodent islets. This group found that human islets show significant variation in islet endocrine cell composition both within and between individuals, but concluded that there is a clear, “non-random clustering of β cells” within human islets, and that blood vessels penetrate these β-cell clusters. Vercollone et al. (2015) investigated the consequences the transgenic overexpression of human EpCAM (Epithelial Cell Adhesion Molecule) under the control of the MMTV-LTR promoter. They observed an enormous increase in islet cell mass with altered architectural organization of α- and δ-cells, suggesting that EpCAM may potentially regulate islet expansion. Rodriguez-Calvo et al. (2015) investigated the pancreas of a double autoantibody-positive human donor at high risk of developing T1D, showing that elevated MHC-I expression and CD8 T cell infiltration are heterogeneously distributed in the islets and differentially affect islets situated in different regions of the pancreas. Brissova et al. (2015) addressed the question of whether vascularization of islets in humans resembles the high degree of vascularization found in mouse islets and whether this arrangement is altered in diabetes. In a quantitative morphometric analysis, they found that human islets have substantially less vascularization than mouse islets, and that the density of islet capillaries is increased in human type 2 diabetes vs. non-diabetic controls. Asadi et al. (2015) aimed to identify and characterize antibodies that can be used to assess proinsulin processing by immunofluorescence staining of islets of different species, including humans. They identified antibodies that are specific for various proinsulin processing products, rodent-specific C-peptides, and human-specific C-peptide or proinsulin. Finally, Meier et al. (2015) address the question of optimal sample size in quantitative morphometric analyses of β cells and amyloid in cultured rodent islets. Their findings are useful for determining optimum sample sizes in the design of studies that use isolated islets to study β-cell morphology and function. These articles showcase the use of state-of-the-art histochemical techniques and imaging technology as powerful experimental approaches for islet biology. The editors express their thanks and appreciation to the authors for contributing excellent articles for this issue.