The paracrine signalling between endothelial and pancreatic β-cells: implications for oxidative stress and diabetes

The Langerhans islets are highly vascularized structures that regulate plasma glucose levels. These islets are primarily composed of different types of endocrine cells (α, β, δ, PP, and ε) and endothelial cells. The paracrine signalling between pancreatic β-cells and endothelial cells is key for maintaining β-cell mass and preserving endocrine function. Oxidative stress, caused by an excess of reactive oxygen species (ROS), is a pathological mechanism that damages pancreatic β-cells and endothelial cells. In this review, we discuss how oxidative stress impacts not only on endothelial and pancreatic β-cells individually, but also on their paracrine signalling. Oxidative stress triggers apoptosis and dysfunction of endothelial and pancreatic β-cells, as well as it alters glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells. Moreover, oxidative stress affects to the homeostasis of vascular endothelial growth factor (VEGF) and Heparin-binding Epidermal Growth Factor (HB-EGF), two key mediators of the β-cell-endothelial cell crosstalk. Finally, an oxidative environment in the Langerhans islets promotes inflammation by increasing the secretion of cytokines, which impact in both cell types, further impairing insulin production. These effects of oxidative stress on the endothelial cell-β-cell paracrine signalling may represent a promising therapeutic target to alleviate diabetes development and its derived complications.