Pericytes modulate islet immune cells and insulin secretion through Interleukin-33 production in mice.

Introduction: Immune cells were recently shown to support β-cells and insulin secretion. However, little is known about how islet immune cells are regulated to maintain glucose homeostasis. Administration of various cytokines, including Interleukin-33 (IL-33), was shown to influence β-cell function.

Development of a 3D atlas of the embryonic pancreas for topological and quantitative analysis of heterologous cell interactions.

Generating comprehensive image maps, while preserving spatial three-dimensional (3D) context, is essential in order to locate and assess quantitatively specific cellular features and cell-cell interactions during organ development. Despite recent advances in 3D imaging approaches, our current knowledge of the spatial organization of distinct cell types in the embryonic pancreatic tissue is still largely based on two-dimensional histological sections. Here, we present a light-sheet fluorescence microscopy approach to image the pancreas in three dimensions and map tissue interactions at key time points in the mouse embryo.

The postnatal pancreatic microenvironment guides β cell maturation through BMP4 production.

Glucose homeostasis depends on regulated insulin secretion from pancreatic β cells, which acquire their mature phenotype postnatally. The functional maturation of β cells is regulated by a combination of cell-autonomous and exogenous factors; the identity of the latter is mostly unknown. Here, we identify BMP4 as a critical component through which the pancreatic microenvironment regulates β cell function.

From virus to diabetes therapy: Characterization of a specific insulin-degrading enzyme inhibitor for diabetes treatment.

Inhibition of insulin-degrading enzyme (IDE) is a possible target for treating diabetes. However, it has not yet evolved into a medical intervention, mainly because most developed inhibitors target the zinc in IDE's catalytic site, potentially causing toxicity to other essential metalloproteases. Since IDE is a cellular receptor for the varicella-zoster virus (VZV), we constructed a VZV-based inhibitor.

Pericytes contribute to the islet basement membranes to promote beta-cell gene expression.

β-Cells depend on the islet basement membrane (BM). While some islet BM components are produced by endothelial cells (ECs), the source of others remains unknown. Pancreatic pericytes directly support β-cells through mostly unidentified secreted factors.

Pancreatic pericytes originate from the embryonic pancreatic mesenchyme.

The embryonic origin of pericytes is heterogeneous, both between and within organs. While pericytes of coelomic organs were proposed to differentiate from the mesothelium, a single-layer squamous epithelium, the embryonic origin of pancreatic pericytes has yet to be reported. Here, we show that adult pancreatic pericytes originate from the embryonic pancreatic mesenchyme.

Pancreas organogenesis: Approaches to elucidate the role of epithelial-mesenchymal interactions.

Pancreas organogenesis depends on proper interactions of endoderm-derived epithelial cells, which will form the exocrine and endocrine cells of the adult organ, with their surrounding mesenchymal layer. Research on the role of pancreatic mesenchyme, pioneered by Golosow and Grobstein in the 1960's, revealed these cells regulate multiple events during pancreas development. Still, much is unknown regards the molecular basis of epithelial-mesenchymal interactions in this process.

Pancreatic Pericytes Support β-Cell Function in a Tcf7l2-Dependent Manner.

Polymorphism in , a component of the canonical Wnt signaling pathway, has a strong association with β-cell dysfunction and type 2 diabetes through a mechanism that has yet to be defined. β-Cells rely on cells in their microenvironment, including pericytes, for their proper function. Here, we show that Tcf7l2 activity in pancreatic pericytes is required for β-cell function.

Neonatal pancreatic pericytes support β-cell proliferation.

Objective: The maintenance and expansion of β-cell mass rely on their proliferation, which reaches its peak in the neonatal stage. β-cell proliferation was found to rely on cells of the islet microenvironment. We hypothesized that pericytes, which are components of the islet vasculature, support neonatal β-cell proliferation.

Isolating and Analyzing Cells of the Pancreas Mesenchyme by Flow Cytometry.

The pancreas is comprised of epithelial cells that are required for food digestion and blood glucose regulation. Cells of the pancreas microenvironment, including endothelial, neuronal, and mesenchymal cells were shown to regulate cell differentiation and proliferation in the embryonic pancreas. In the adult, the function and mass of insulin-producing cells were shown to depend on cells in their microenvironment, including pericyte, immune, endothelial, and neuronal cells.

Islet Pericytes Are Required for β-Cell Maturity.

β-Cells rely on the islet microenvironment for their functionality and mass. Pericytes, along with endothelial cells, make up the dense islet capillary network. However, although the role of endothelial cells in supporting β-cell homeostasis has been vastly investigated, the role of pericytes remains largely unknown.