Obiettivo
Various alterations of metabolism are a central characteristic of physiological disorders and diseases, including cancer, obesity, type 2 diabetes (T2D) and the metabolic syndrome (MS) and are as such a major burden on national budgets. Thus, there is an urgent need to further understand the various processes that determine the occurence of metabolic alterations, predominantly obesity and T2D and to develop strategies to provide therapeutic aid. Several intrinsic factors either predetermine or correlate with the occurence of obesity and the development of T2D and MS. Our laboratory has recently reported a yet unidentified role of the mammalian oxygen sensor PHD1 in the control of glucose homeostasis by phenotyping PHD1 knockout mice. In detail, loss of PHD1 lowers oxygen consumption in skeletal muscle by shifting glucose metabolism from oxidative to more anaerobic ATP production which impairs oxidative muscle performance in healthy conditions, but induces hypoxia tolerance and protects myofibers against lethal ischemia. In addition, novel findings suggest a correlation between PHD1 and intrinsic obesity and T2D related factors. To extend our studies on PHD specific metabolic alterations we will utilize several in the lab made transgenic PHD mice to address the followong issues (i) assess obesity and T2D related changes in lipid and glucose homeostasis in mice lacking each of the PHDs either constitutively or specifically in key metabolic tissues by comparing various metabolic parameters before and after administration of a high fat diet (ii) determine the consequences of loss of PHD function in pancreatic ß-cell physiology, insulin signalling and glucose tolerance using a mouse model of dietary induced diabetes and (iii) determine whether loss of PHD function might have any potential for pharmaceutical intervention by intercrossing our PHD deficient mouse strains with well established mouse models to study obesity and obesity related disorders such as T2D and MS.
Campo scientifico
- medical and health sciencesclinical medicineendocrinologydiabetes
- engineering and technologyelectrical engineering, electronic engineering, information engineeringelectronic engineeringsensors
- medical and health sciencesclinical medicineoncology
- medical and health sciencesbasic medicinephysiologyhomeostasis
- medical and health scienceshealth sciencesnutritionobesity
Parole chiave
Argomento(i)
Invito a presentare proposte
FP7-PEOPLE-2007-2-1-IEF
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Meccanismo di finanziamento
MC-IEF - Intra-European Fellowships (IEF)Coordinatore
9052 ZWIJNAARDE - GENT
Belgio