Objectif
Diabetes is a devastating illness declared by the World Health Organization as the XXI century epidemic. It is urgent to define the factors contributing to diabetes onset and severity, and to identify new potential therapies to prevent and treat diabetes and its complications. Type 2 diabetes develops through a multi-stage process. The body becomes unable to use insulin effectively and the pancreatic beta cells try to compensate producing more insulin, a condition known as insulin resistance. Eventually the beta cells become exhausted and cannot produce enough insulin to overcome insulin resistance. At this point, this condition frequently progresses to diabetes. Diabetes develops after a substantial decrease in the number of beta cells (increase in cell death/decrease in proliferation and neogenesis) and/or the impairment of insulin secretion needed to maintain euglycemia. The molecular mechanisms by which beta cells fail to compensate for insulin resistance remain elusive. The aims are: 1) Identification of the molecular mechanisms that lead to impaired beta cell proliferation in the pathophysiology of type 2 diabetes. 2) Therapeutic role of beta-cell proliferation in the treatment of type 2 diabetes. To address aim 1, db/db mice deficient for the leptin receptor on a C57BLKS/J background (a genetic model of obesity that develops diabetes) will be used. The techniques chosen for this aim include: proliferation studies; identification and quantification of cell cycle control proteins (western-blot, RT-PCR and immunofluorescence); techniques to study glucose/insulin homeostasis (glucose/insulin levels, glucose tolerance test and insulin tolerance test). To address aim 2, adenoviral vectors that contain cDNA of cell cycle activators (cyclin C, cyclin D1, D2, D3, cyclin E and their associated kinases cdk-3, -4 and -2) will be injected through the pancreatic duct in mice prone to develop diabetes (as in aim 1). The techniques will be similar to the ones in aim
Champ scientifique
- medical and health sciencesbasic medicinephysiologypathophysiology
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesclinical medicineendocrinologydiabetes
- medical and health sciencesbasic medicinephysiologyhomeostasis
- 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
11009 Cadiz
Espagne