Role of central glucagon-like peptide-1 in stress regulation

PHYSIOLOGY & BEHAVIOR

卷:122

Review

Ghosal, Sriparna¹  Myers, Brent¹  Herman, James P.¹ 

[1] Univ Cincinnati, Dept Psychiat & Behav Neurosci, Cincinnati, OH 45237 USA

关键词: Anxiety;    Chronic stress;    HPA axis;    Preproglucagon;    Nucleus of the solitary tract;    Paraventricular nucleus;   

DOI  :  10.1016/j.physbeh.2013.04.003

来源: Elsevier

【 摘 要 】

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. (C) 2013 Elsevier Inc. All rights reserved.

【 授权许可】

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