Impact of cholinergic innervation in the pancreatic vasculature

Abstract

Pancreatic islets consist of several secretory cells, with an emphasis on beta cells, responsible for insulin production and secretion. Beta cells are of great interest to study because their failure or death is the major cause of diabetes. Islets are also composed of vascular and neural cells, and each cell type is essential for the regulation and maintenance of islet function and, therefore, glucose homeostasis. Pancreatic islets are highly vascularized, and there is a positive correlation between blood flow to the islet and the activity of endocrine cells. Intrapancreatic neurons appear to be mandatory relays for descending vagal input and are the local providers of acetylcholine, a powerful modulator of islet function. Activation of intrapancreatic neurons has recently been shown to modulate glucose homeostasis in mice. Although blood vessels and neurons are natural candidates as effectors coordinating pancreas function, their regulatory role has not been addressed experimentally. Therefore, the aim of the study is to elucidate the cholinergic innervation pattern and its effect on the pancreatic microvessels. To do that, we will determine the impact of cholinergic signaling on pericytes' Ca2+ responses and capillary diameter and we will perform a neuroanatomical tracing and electric stimulation of cholinergic neurons in living pancreas slices from mice. Developing this project will allow us to advance the understanding of how vascularization in pancreatic islets is regulated, focusing on the role of cholinergic innervation and input in pancreatic microvessels. Upon returning to Brazil, we will be able to apply this knowledge to studying this regulation in models of malnutrition.