Identifier

etd-01062005-142505

Degree

Doctor of Philosophy (PhD)

Department

Human Ecology

Document Type

Dissertation

Abstract

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.

Date

2005

Document Availability at the Time of Submission

Release the entire work immediately for access worldwide.

Committee Chair

Roy J Martin

Included in

Human Ecology Commons

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