Endocrine cells in pancreatic islets are embedded in a network of blood vessels that support adequate nutrient sensing, efficient release of hormones, and timely responses to changes in glycemia. This network of islet blood vessels consists of capillary tubes made of endothelial cells that are covered by pericytes. Compelling evidence indicates that significant structural alterations of islet blood vessels occur in individuals with T1D. These include not only changes in blood vessel diameter and density, altered expression of adhesion molecules by endothelial cells, but also perivascular alterations such as increased infiltration of immune cells, and altered composition of the extracellular matrix. Pericytes are part of the pancreatic islet vascular niche but it is not known what happens to them during T1D progression. The aim of this research project is to investigate pericytes and examine their phenotype and response profile in islets from non-diabetic donors as well as in individuals at different stages of T1D. Based on recent preliminary data obtained using nPOD material (under the parent project; see below), our hypothesis is that islet pericyte dysfunction early on in the disease impairs microvascular function, favoring immune cell infiltration and contributing to the development of T1D.
