Year: 2017
Type: dissertation
Abstract: The mediobasal hypothalamus (MBH) and the dorsal vagal complex (DVC) regions contain a leaky blood-brain barrier and therefore act as critical sites of action for circulating hormones and nutrients on glucose and energy homeostasis. For example, hormones such as insulin, leptin and glucagon and nutrients such as lipids, glucose and amino acids act in the MBH and DVC to regulate hepatic glucose production, glucose tolerance, food intake and body weight, but the underlying CNS sensory mechanisms in rodents and humans remain elusive. The current dissertation unveils novel mechanisms for glucagon action in the MBH and glycine sensing in the DVC in rats and mice that maintain glucose and energy homeostasis. In Study 1, we discovered that KATP channel is necessary for MBH glucagon action to exert glucose control. In Study 2, we found that pharmacological and molecular manipulation of glycine transporter 1 in the DVC enhances glycine sensing and potently regulates glucose and energy homeostasis. In conclusion, I have discovered novel mechanisms for glucagon and glycine sensing in the brain that regulate glucose and energy homeostasis, and have unveiled CNS therapeutic targets for diabetes and obesity.
Source: TSpace (University of Toronto)
Author: Mona A. Abraham
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2897045702