The identification of new molecular targets that could lead to new therapeutics for NIDDM is an important goal, which can be achieved under defined experimental conditions with strategies that combine genomic and proteomic approaches. In the present study we have used a proteomics approach to identify such targets. Lean and obese C5? B1/6J lep/lep mice were given BRL49653, rosiglitazone, 10mg/kg diet, by dietary admixture for 7 days. Rosiglitazone normalized the impaired glucose tolerance in lep/lep mice but had no significant effect in the lean mice. Samples of liver, liver nuclei, muscle, WAT, BAT and islets were arrayed in a two-dimensional electrophoresis system that separated 2500 individual spots. Image analysis allowed the detection of 94 significant (p<0.05) differentially expressed polypeptides in obese relative to lean controls. Thirty six of these were significantly (p<0.05) modulated in obese models to the level in lean control after rosiglitazone treatment Forty three of them were identified by mass spectrometry (MALDI- and/or Q-TOF-MS). Several of these differentially expressed proteins were components of fatty acid and carbohydrate metabolism and others are new unknown proteins. The understanding of the biomolecular pathways and interactions of these new proteins will be essential in further studies to define their biological function. In conclusion, proteomic approaches should provide in the near future new clues for the elucidation of the pathogenesis of the various defects involved in type 2 diabetes and provide major insights into new more effective treatments.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:601372 |
| Date | January 2000 |
| Creators | Sanchez, Jean Charles |
| Publisher | University of Buckingham |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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