The purpose of this project is to assess the regulation of glucose transporter gene expression by glucose, to identify the CCAAT/enhancer-binding proteins (C/EBP) implicated in the control of glucose transporter genes, and to test whether the nonoxidative branch of the pentose phosphate pathway might be critical for glucose-mediated metabolic gene expression. Fully-differentiated 3T3-L1 adipocytes in culture were subjected to four experimental conditions: elevated glucose feeding (25mM), glucose deprivation, use of non-metabolized glucose analogs, and xylitol. Northern blot analysis were conducted to determine the level of expression of various metabolic regulation genes. A coordinate regulation of C/EBPalpha and GLUT-4 mRNA levels was observed in all the culture conditions tested. In contrast, C/EBPa and GLUT-1 expression changed little over the course of the experiments while gadd153 gene was induced to high level in response to glucose starvation. It appears that phosphorylation of glucose to glucose-6-phosphate is indispensable for its transcriptional action on C/EBP? and GLUT-4 genes. Evidence that the non-oxidative branch of the pentose phosphate pathway is involved in glucose-mediated regulation of gene expression is presented.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Intramural Research (Z01)
Project #
1Z01AG000887-02
Application #
2565787
Study Section
Special Emphasis Panel (LCP)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1996
Total Cost
Indirect Cost
Name
National Institute on Aging
Department
Type
DUNS #
City
State
Country
United States
Zip Code