Over the past 25 years, obesity and diabetes have increased to near pandemic levels. Both obesity and diabetes are characterized by a dysfunction in the central regulation of energy balance. Arcuate (ARC) glucose sensing neurons (GSNs) are ideally situated to serve as the neuronal substrate which confers the brain with the ability to sense and respond to changes in glucose levels. These neurons are regulated by the critical signals of whole body energy balance, insulin and leptin. Our data show that the nature of the insulin effect varies with extracellular glucose. Furthermore, our data implies that insulin decreases the glucose sensitivity of ARC GSNs. Fatty acids also serve as a signal of energy homeostasis in the ARC. While, the acute effects of these nutrient and hormonal signals of peripheral energy homeostasis have been examined their effects on the glucose sensitivity of ARC GSNs remains to be defined. This proposal will test the overall hypothesis that the activity/glucose sensitivity of ARC GSNs is determined by the nutrient and hormonal milieu. Furthermore, dysruption in insulin and leptin signaling seen during obesity impairs ARC GSNs. This may contribute to the dysfunctional central regulation of energy balance. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31NS056815-02
Application #
7261296
Study Section
Special Emphasis Panel (ZRG1-F06-J (20))
Program Officer
Mitler, Merrill
Project Start
2006-07-01
Project End
2009-06-30
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
2
Fiscal Year
2007
Total Cost
$28,790
Indirect Cost
Name
University of Medicine & Dentistry of NJ
Department
Pharmacology
Type
Schools of Medicine
DUNS #
623946217
City
Newark
State
NJ
Country
United States
Zip Code
07107