Abstract 16543: Reducing Insulin-like Growth Factor-1 Receptor Expression Improves Vascular Repair and Regeneration in Whole Body Insulin Resistance

IntroductionInsulin resistance is an independent risk factor for cardiovascular disease. We have previously shown that the insulin-like growth factor-1 receptor (IGF-1R) is a negative regulator of insulin receptor (IR) signalling, by sequestering IR subunits in insulin resistant IR:IGF-1R ‘hybrid receptors’. By crossing IR haploinsufficient (IRKO) mice with IGF-1R haploinsufficient (IGF-1RKO) mice (producing “double knockout” or DKO mice), we have previously demonstrated rescue of the endothelial dysfunction caused by insulin resistance. Whether this is associated with wider benefits in vascular biology is unclear.HypothesisReducing expression of the IGF-1R in whole body insulin resistance improves vascular repair and regeneration.MethodsMetabolic assessment included measurement of weight gain and glucose and insulin tolerance testing. Denuding femoral artery endothelial injury was induced with angioplasty guidewire and repair was quantified by Evans Blue perfusion 4 days later. For hindlimb ischemia, the left femoral artery was ligated and excised, with sham surgery contralaterally. Control:ischemic limb perfusion ratio was assessed with weekly laser Doppler imaging for 4 weeks. Data are expressed as mean (standard error) and compared using t-tests; * denotes p