| Pancreatic beta-cells are the mammals' only cell type that produce insulin, a hormone responsible for triggering the storage of soluble nutrients absorbed from diet into insoluble, energy-rich products such as glycogen, protein, and fats. The beta-cell possesses an intrinsic mechanism for sensing glucose that results in the stimulated secretion of insulin from the cell's insulin stores. Additionally, it is well-documented that the nervous innervations of the pancreas serve a regulatory function over several aspects of pancreatic endocrine physiology- particularly that which occurs at the pancreatic islet, such as the alpha-cell secretion of glucagon- a counter-regulatory hormone responsible for the stimulation of hepatic glucose production under hypoglycemia as well as a feedback bolster of insulin release by beta-cells to more effectively promote nutrient storage postprandially. Exposing pancreatic islets to the sympathetic neurotransmitter epinephrine results in an inhibition of insulin secretion. Conversely, the parasympathetic neurotransmitter acetylcholine enhances insulin secretion beyond the levels that stimulatory glucose can alone. However, the neuronal connections between the endocrine pancreas and the central nervous system are largely unknown.;The present work proposes that the central nervous system plays a critical role in the regulation of pancreatic islet physiology in response to nutrient load- mainly at the hypothalamic nuclei. To address this central hypothesis, this work is partitioned into two related projects: 1) the establishment of the hypothalamic nuclei as an end-point in the humoral detection of circulating nutrients and hormones for autonomic reflex adjustments in endocrine pancreas hormones and 2) the manipulation of glucose sensing in discrete hypothalamic areas in order to characterize each area's contribution to the regulation of endocrine pancreas physiology and overall glucose homeostasis in a mouse model. |
