It has been proposed that the glucose sensing mechanism in the hypothalamus and hindbrain is similar to pancreatic â cells, and brain glucose sensing may be involved in the regulation of food intake. For the first part of the dissertation, it is proposed that molecules involved in â-cell glucose sensing, including glucokinase (GK), glucose transporter GLUT2, sulfonylurea receptor-1 (SUR1), glucagon-like peptide-1 receptor (GLP-1R), and the feeding-related neuropeptide Y (NPY), are colocalized in specific areas in the hypothalamus and hindbrain. GK, GLUT2, SUR1, GLP-1R and NPY mRNA expression in ten discrete brain areas were quantified by real time RT-PCR, which will serve as an initial step for the next functional study.
The second part of the dissertation has been focused on GLUT2 only and it is proposed that brain GLUT2 may play a role in the central glucose sensing, specifically, brain GLUT2 is regulated by energy / glucose status and overexpression of GLUT2 in neuronal cells will alter cellular energy status and feeding related neuropeptide expression. Under three conditions: in vivo, ex vivo and in vitro, GLUT2 mRNA was significantly upregulated in the area postrema (AP) in the two-week 50% underfed rats, and by 1 mM glucose in rat area postrema / nucleus of the solitary tract (AP/NTS) tissue culture as well as in N1E-115 neuroblastoma cell culture. Next, rat liver GLUT2 were overexpressed in GT1-7 neuroblastoma cells. Compared with control cells, GLUT2 overexpression resulted in significantly increased cellular ATP levels at 5 mM or higher glucose concentrations, greater inhibition of AgRP mRNA by 25 mM glucose, and attenuated AgRP mRNA stimulation by 2DG. In summary, brain GLUT2 mRNA is upregulated by low energy and low glucose status; overexpression of GLUT2 in neuronal cells results in higher cellular energy status and greater suppression of hunger signals at high glucose levels or during glucoprivation. The conclusion is that brain GLUT2 is likely to play a role in the central glucose sensing and may be involved in the regulation of food intake.
| Identifer | oai:union.ndltd.org:LSU/oai:etd.lsu.edu:etd-01062005-142505 |
| Date | 07 January 2005 |
| Creators | Li, Bing |
| Contributors | Roy J Martin, Maren Hegsted, Yan Chen, J Marcos Fernandez, Joseph Taboada, David S Roane |
| Publisher | LSU |
| Source Sets | Louisiana State University |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lsu.edu/docs/available/etd-01062005-142505/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached herein a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to LSU or its agents the non-exclusive license to archive and make accessible, under the conditions specified below and in appropriate University policies, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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