title: Role of central glucagon-like peptide-1 in stress regulation.
abstract: Glucagon-like peptide 1 (GLP-1) is best known as an incretin hormone, secreted from L cells in the intestine in response to nutrient ingestion to stimulate glucose-dependent insulin secretion. However, GLP-1 is also expressed in neurons, and plays a major role in regulation of homeostatic function within the central nervous system (CNS). This review summarizes our current state of knowledge on the role GLP-1 plays in neural coordination of the organismal stress response. In the brain, the primary locus of GLP-1 production is in the caudal nucleus of the solitary tract (NTS) and the ventrolateral medulla of the hindbrain. GLP-1 immunoreactive fibers directly innervate hypophysiotrophic corticotropin-releasing hormone (CRH) neurons in the hypothalamic paraventricular nucleus (PVN), placing GLP-1 in prime position to integrate hypothalamo-pituitary-adrenocortical responses. Exogenous central GLP-1 activates HPA axis stress responses, and responses to a variety of stressors can be blocked by a GLP-1 receptor (GLP-1R) antagonist, confirming an excitatory role in glucocorticoid secretion. In addition, central infusion of GLP-1R agonist increases heart rate and blood pressure, and activates hypothalamic and brainstem neurons innervating sympathetic preganglionic neurons, suggesting a sympathoexcitatory role of GLP-1 in the CNS. Bioavailability of preproglucagon (PPG) mRNA and GLP-1 peptide is reduced by exogenous or endogenous glucocorticoid secretion, perhaps as a mechanism to reduce GLP-1-mediated stress excitation. Altogether, the data suggest that GLP-1 plays a key role in activation of stress responses, which may be connected with its role in central regulation of energy homeostasis.
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Reading Campus, OH 45237-0506, USA. Electronic address: ghosalsa@mail.uc.edu.
authors.forename: Sriparna
authors.initials: S
authors.lastname: Ghosal
authors.forename: Brent
authors.initials: B
authors.lastname: Myers
authors.forename: James P
authors.initials: JP
authors.lastname: Herman
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism / Q000502:physiology*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D010913:Pituitary-Adrenal System / Q000378:metabolism*; D013312:Stress, Physiological / Q000502:physiology*; D013315:Stress, Psychological / Q000378:metabolism*
chemical_list: D052216:Glucagon-Like Peptide 1
keywords: Anxiety; Chronic stress; HPA axis; Nucleus of the solitary tract; Paraventricular nucleus; Preproglucagon