Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


ucin1148315063.pdf (16.97 MB)

ETD Abstract Container

Abstract Header

THE ROLE OF GLUCAGON-LIKE PEPTIDE-1 IN STRESS AND ENERGY HOMEOSTASIS

TAUCHI, MIYUKI
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1148315063

Abstract Details

2006, PhD, University of Cincinnati, Medicine : Neuroscience/Medical Science Scholars Interdisiplinary.
The hypothalamo-pituitary-adrenocortical (HPA) axis is a final regulator of stress responses, which are activated by non-specific stressful stimuli. Albeit acute activation of the HPA axis is protective to fight against noxious stimuli, prolonged activation can be deleterious. Glucagon-like peptide-1 (7-36) amide (GLP-1) is an insulinotropic intestinal peptide, which is also expressed in brain. GLP-1 expression in brain is restricted in the nucleus of solitary tract and the ventrolateral medulla of the brainstem. GLP-1 nerve fibers innervate widely in brain. Centrally infused GLP-1 is known to activate the HPA axis. Thus, in this dissertation, we aimed to understand the role of GLP-1 in stress. First, the GLP-1 system in stress circuitry was investigated using immunohisochemical methods. We found heavy GLP-1 innervation of hypothalamic neurons expressing corticotropin releasing hormone, and oxytocin, as well as preautonomic neurons projecting the brainstem. There was scarce innervation of argininvasopressin expressing neurons. The distribution suggests that GLP-1 activates the HPA axis not only directly, but can also modulate it via other systems. Next, we monitored a regulation of GLP-1 gene expression by acute stress. In situ hybridization was performed using riboprobes generated by targeting mRNA and intronic RNA. We found that GLP-1 messenger level is quickly down-regulated after stress. In addition, intronic RNA expression revealed that the activation was restricted to the lateral area of the nucleus of solitary tract, which projects to the paraventricular nucleus of thalamus. Furthermore, we tested the role of GLP-1 in chronic stress. We found that GLP-1 is required for animals to develop a chronic stress-induced facilitated response to a novel stressor. In addition, GLP-1 systems interacted with stress to reduce body weight. Finally, as an effort to elucidate possible mechanisms for the interaction between chronic stress and GLP-1, the anorectic effects of GLP-1 and glucose were tested. We found that the co-administration of glucose and GLP-1 synergistically increased anorectic effects, and the blockade of GLP-1 completely abolished the anorectic effect elicited by glucose. We concluded that GLP-1 is particularly important for chronic stress-induced stress facilitation, and suggest that GLP-1 may play an important role to link chronic stress and energy homeostasis.
Dr. James Herman (Advisor)
167 p.
Biology, Neuroscience

Recommended Citations

Citations

  • TAUCHI, M. (2006). THE ROLE OF GLUCAGON-LIKE PEPTIDE-1 IN STRESS AND ENERGY HOMEOSTASIS [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1148315063

    APA Style (7th edition)

  • TAUCHI, MIYUKI. THE ROLE OF GLUCAGON-LIKE PEPTIDE-1 IN STRESS AND ENERGY HOMEOSTASIS. 2006. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1148315063.

    MLA Style (8th edition)

  • TAUCHI, MIYUKI. "THE ROLE OF GLUCAGON-LIKE PEPTIDE-1 IN STRESS AND ENERGY HOMEOSTASIS." Doctoral dissertation, University of Cincinnati, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1148315063

    Chicago Manual of Style (17th edition)

ucin1148315063
505
© 2006, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.