Objective
Thiazolidinediones (TZDs) are clinically proven insulin sensitizers with anti-inflammatory benefits used in the therapy of type 2 diabetes mellitus (T2DM) and atherosclerosis. TZDs can activate a transcription factor, the peroxisome proliferator-activated receptor gamma (PPARg). PPARg regulates expression of several genes involved in inflammatory pathways, lipid transport and carbohydrate metabolism. Antidiabetic effects of TZDs have been coupled to macrophages, since tissue macrophages can produce inflammatory mediators which can reduce insulin sensitivity leading to T2DM and its cardiovascular complications. Administration of TZDs spreaded rapidly recently, although serious secondary effects as fluid retention and ischemic heart disease have questioned the clear benefits of non-selective PPAR activation by TZDs in the medication of T2DM and related disorders. Kidney PPAR positively regulates sodium and water resorbtion, therefore TZD-induced fluid retention can be due to the activation of PPARγ in the kidney collecting ducts. Fluid retention can lead to backward heart failure, therefore we think that kidney PPAR is the origin of unwanted cardiac TZD effects. To test this novel hypothesis we propose a cross-disciplinary research project involving molecular genetics, in vivo imaging, and gene engineered animal models targeting the molecular mechanisms behind the cardiovascular complications of TZDs. We will determine also the contribution of tissue specific PPAR mutations to water retention and ischemic heart disease. Molecular mechanisms behind T2DM and its cardiovascular complications are among the most important and timeliness research areas in Europe, due to the growing T2DM prevalence. Understanding TZD side effects will contribute to new treatment strategies of T2DM. The success of this proposal will increase European competitiveness and will produce long term synergies and structuring community research effects.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciencesbiological sciencesmolecular biologymolecular genetics
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugs
- medical and health sciencesclinical medicinecardiologycardiovascular diseasesarteriosclerosis
- medical and health sciencesclinical medicineendocrinologydiabetes
- natural sciencesbiological sciencesbiochemistrybiomoleculescarbohydrates
You need to log in or register to use this function
We are sorry... an unexpected error occurred during execution.
You need to be authenticated. Your session might have expired.
Thank you for your feedback.
You will soon receive an email to confirm the submission. If you have selected to be notified about the reporting status, you will also be contacted when the reporting status will change.
Keywords
Topic(s)
Call for proposal
FP7-PEOPLE-IEF-2008
See other projects for this call
Funding Scheme
MC-IEF - Intra-European Fellowships (IEF)Coordinator
28029 Madrid
Spain