Methods and compositions for modulating gluconeogenesis using PGC-1
The invention provides novel methods and compositions for modulating gluconeogenesis through modulation of PGC-1 activity or expression. Also provided are methods for identifying compounds that modulate gluconeogenesis through modulation of PGC-1 activity or expression, as well as methods for identifying compounds that modulate the interaction of PGC-1 with PGC-1 target molecules. Further provided are methods for treating disorders characterized by aberrant gluconeogenesis.
1. A method for identifying a compound capable of modulating gluconeogenesis comprising:
a) contacting a cell with a compound; and
b) assaying the ability of the compound to modulate the expression of a PGC-1 nucleic acid molecule by measuring the PGC-1 nucleic acid molecule level or the activity of a PGC-1 polypeptide by measuring the PGC-1 polypeptide level or by measuring the PGC-1 polypeptide activity
to thereby identify a compound that modulates gluconeogenesis.
2. The method of claim 1 , wherein PGC-1 expression or activity is increased.
3. The method of claim 1 , wherein PGC-1 expression or activity is decreased.
4. The method of claim 1 , wherein PGC-1 expression is measured by Northern blotting, in situ hybridization, enzyme linked immunosorbent assay, Western blotting, immunoprecipitations, or immunofluorescence.
5. The method of claim 1 , wherein expression is measured by Northern blotting.
6. The method of claim 1 , wherein the cell is a hepatocyte.
7. The method of claim 6 , wherein the hepatocyte is selected from the group consisting of a primary hepatocyte and a Fao hepatoma cell.
8. A method for identifying a compound capable of modulating gluconeogenesis comprising:
a) contacting a cell with a compound; and
b) assaying the ability of the compound to modulate the expression of a PGC-1 nucleic acid molecule by Northern blotting
to thereby identify a compound that modulates gluconeogenesis.