Objectif
Insulin resistance is a hallmark of human diseases, including diabetes and obesity, which lead to abnormal glucose and lipid metabolism as a result of impaired metabolic response to insulin. The mechanism underlying the development of insulin resistance remains incompletely understood. Excessive production of pro-inflammatory cytokines by the adipose tissue is linked to insulin resistance. Hepatocyte Growth Factor (HGF) is an adipocytokine elevated in obese subjects, which strongly correlated with the metabolic syndrome. However the role of HGF in the etiology of the insulin resistance remains unknown. Recently, we have demonstrated that HGF is a potent activator of glucose transport and metabolism, and also a strong inhibitor of fatty acid oxidation in rodent myotubes (Perdomo et al., J. Biol. Chem., 2008). In addition, we have generated (i) a conditional transgenic mouse of HGF in the skeletal muscle, and (ii) a conditional knockout mouse of the HGF receptor (c-met) in skeletal muscle. We hypothesized that HGF ameliorates skeletal muscle insulin resistance in vivo. To test this hypothesis, we propose two aims: 1) To investigate the relationship between plasma HGF levels and insulin resistance in humans. 2) To investigate the role of HGF in the insulin-resistant skeletal muscle. Accomplishing this project will elucidate the relationship between plasma HGF levels and insulin resistance in humans and determine its contribution to the etiology and pathophysiology of insulin resistance. A mechanistic understanding of insulin resistance will facilitate the development of therapeutic strategies and identification of new drug targets in the prevention and treatment of diabetes and obesity. Finally, my preliminary data have provided feasibility for the project.
Champ scientifique
- medical and health sciencesbasic medicinephysiologypathophysiology
- natural scienceschemical scienceselectrochemistryelectrolysis
- medical and health sciencesclinical medicineendocrinologydiabetes
- natural sciencesbiological sciencesbiochemistrybiomoleculeslipids
- medical and health scienceshealth sciencesnutritionobesity
Appel à propositions
FP7-PEOPLE-2009-RG
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Régime de financement
MC-IRG - International Re-integration Grants (IRG)Coordinateur
13071 Ciudad Real
Espagne