Objective More than 30 million people are living with diabetes in the EU, with a prevalence expected to grow to over 10% of the adult population by the year 2030. Type 2 diabetes is a major cause of cardiovascular disease related death and disability, substantially increasing the risk of myocardial infarction, stroke and peripheral arterial disease. Recent landmark trials, showing that intensive glucose control does not improve cardiovascular outcomes and may increase mortality in some circumstances, provide a compelling rationale for intense research aimed at developing novel therapeutic strategies. Type 2 diabetes is underpinned by resistance to the effects of insulin, which I have shown in endothelial cells causes reduced bioavailability of the anti-atherosclerotic molecule nitric oxide and leads to accelerated atherosclerosis. The cellular effects of insulin are mirrored by insulin-like growth factor factor-1, the bioavailability of which at its receptor is in turn is regulated by a family of high affinity binding proteins (IGFBP). Epidemiological studies demonstrate and inverse association between one of these binding proteins, IGFBP1, and diabetes-related cardiovascular risk. I have recently demonstrated that IGFBP1 when expressed in mice can ameliorate insulin resistance, obesity and atherosclerosis. In endothelial cells, I showed that IGFBP1 upregulates the production of nitric oxide indepenedently of IGF. These findings suggest that IGFBP1 may be a ‘protective’ endogenous protein and that increasing circulating levels may be a therapeutic strategy to prevent development of diabetes and cardiovascular disease. In this proposal I will address this hypothesis by employing state of the art studies in cells and novel gene modified mice to unravel the molecular basis of the protective effects of IGFBP1 and to investigate the possibility of exploiting the IGF-IGFBP axis to prevent cardiovascular disease in the setting of diabetes and obesity. Fields of science medical and health sciencesclinical medicineangiologyvascular diseasesmedical and health sciencesclinical medicinecardiologycardiovascular diseasesarteriosclerosisnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesclinical medicineendocrinologydiabetesmedical and health scienceshealth sciencesnutritionobesity Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-SG-LS4 - ERC Starting Grant - Physiology, Pathophysiology and Endocrinology Call for proposal ERC-2012-StG_20111109 See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Host institution UNIVERSITY OF LEEDS EU contribution € 1 493 543,00 Address WOODHOUSE LANE LS2 9JT Leeds United Kingdom See on map Region Yorkshire and the Humber West Yorkshire Leeds Activity type Higher or Secondary Education Establishments Administrative Contact Benjamin Williams (Mr.) Principal investigator Stephen Bentley Wheatcroft (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all UNIVERSITY OF LEEDS United Kingdom EU contribution € 1 493 543,00 Address WOODHOUSE LANE LS2 9JT Leeds See on map Region Yorkshire and the Humber West Yorkshire Leeds Activity type Higher or Secondary Education Establishments Administrative Contact Benjamin Williams (Mr.) Principal investigator Stephen Bentley Wheatcroft (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data