Diabetes late complications caused by iron-induced reactive oxygen radicals (A02)

在过去的资助时期，我们证明了2型糖尿病患者和相应的小鼠模型显示出全身铁水平增加。铁蓄积导致产生活性氧物种，降低肝脏对胰岛素的敏感性，并增加糖尿病晚期并发症。具体地说，我们发现非转铁蛋白结合铁(NTBI)会加剧易患动脉粥样硬化的小鼠的动脉粥样硬化进展(ApoE-/-；FPNwt/C326S)，并加强铁超载患者的血管损伤。在第三个资助期，我们将应用新的最先进的药理学策略来重建正常的全身铁水平，以增强胰岛素敏感性并限制糖尿病相关的动脉粥样硬化。

In the past funding periods we demonstrated that patients with type2 diabetes and corresponding mouse models show increased systemic iron levels. Iron accumulation leads to the production of reactive oxygen species, reduces insulin sensitivity in the liver and enhances diabetic late complications. Specifically, we showed that non-transferrin-bound iron (NTBI) exacerbates progression of atherosclerosis in mice susceptible to atherosclerosis (ApoE-/- ;FPNwt/C326S) and enhances vascular damage in patients with iron overload. In the third funding period we will apply novel state-of-the-art pharmacological strategies to re-establish normal systemic iron levels to enhance insulin sensitivity and limit diabetic-related atherosclerosis.