Inhibition of s6 kinaze activity for the treatment of insulin resistance
OwnerJohan Auwerx, Francesca Frigerio +7inventors
InventorsJohan Auwerx, Francesca Frigerio, Stefan Fumagalli, Sara Kozma, Frederic Picard, Melanie Sticker-Jantscheff, George Thomas, Sung Um, Mitsuhiro Watanabe
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Abstract
This invention provides screening methods for agents effective in treating insulin resistance through specific inhibition of S6 kinase 1 activity. Also provided are methods of treating insulin resistance by administering an effective amount of an inhibitor specific for S6 kinase 1.
Claims21
A method of identifying an agent effective in treating insulin resistance, said method comprising the steps of:
- i) incubating S6 kinase with a compound;
- ii) detecting S6 kinase activity;
- and
- iii) determining a compound-induced modulation in the S6 kinase activity relative to when said compound is absent, wherein an alteration of the S6 kinase activity in the presence of the compound is indicative of an agent effective in treating insulin resistance.
A method of screening for an agent effective in treating insulin resistance, the method comprising
- (a) contacting transcriptionally active cellular components with a nucleic acid encoding an S6K gene operably linked to a promoter sequence or an S6K promoter sequence operably linked to a reporter gene in the presence of at least one compound;
- and
- (b) detecting an effect of said compound on S6 kinase expression or S6 kinase promoter activity, wherein detection of a modulation in S6 kinase expression or promoter activity is indicative of an agent effective in treating insulin resistance.
A method for reducing insulin resistance, said method comprising contacting an adipocyte, myocyte or hepatocyte with an effective amount of an S6 kinase 1 inhibitor.
A method for treating or preventing the development of insulin resistance or diabetes, comprising administering to a subject a pharmaceutically effective amount of an S6 kinase modulator.
A method of diagnosing insulin resistance or a predisposition to insulin resistance, comprising:
- (a) detecting the level of S6 kinase activity in a sample from a mammal;
- and
- (b) correlating a change in S6 kinase activity when compared to a normal control value or range of values with insulin resistance or a predisposition to insulin resistance.
Dependencies are inferred from the claim text.