Department of Urology, Urology Research Center, The University of Toledo, Toledo, OH 43614, USA.
Int J Mol Med. 2012 Jan;29(1):3-11. doi: 10.3892/ijmm.2011.810. Epub 2011 Oct 11.
Obesity and diabetes once considered 'rich man's diseases' are one of the biggest public health challenges of the 21st century. Obesity being a gateway to diabetes is a global problem. The supporting statistics are alarming since diabetes is reaching pandemic proportion all over the world. Eighty percent of all patients with diabetes live in developing countries. In this review we describe the role of plasminogen activator inhibitor type one (PAI-1) in the pathology of obesity and diabetes and its potential to be a target in therapy. PAI-1 is the fast acting and specific inhibitor of tissue plasminogen activator (tPA) and urokinase (uPA), the activators of plasminogen and consequently of fibrinolysis. In obesity and diabetes it has been linked to the increased incidence of thrombosis. However, PAI-1 is also involved in the regulation of other proteins engaged in hemostasis. These molecules include transforming growth factor β (TGF-β), tumor necrosis factor α (TNF-α), angiotensin II and interleukin 6 (IL-6), all of which up-regulate PAI-1 in various cell types or can be up-regulated by PAI-1. Thus, PAI-1 plays a critical role in the insulin resistance syndrome, which leads to type 2 diabetes mellitus, and is associated with its side effects such as an increased risk of diabetic nephropathy, atherosclerotic cardiovascular disease and others. Thus inactivating of PAI-1 or increasing its clearance can alleviate the burden of obesity and diabetes.
肥胖和糖尿病曾经被认为是“富人病”，是 21 世纪最大的公共卫生挑战之一。肥胖是糖尿病的一个入口，这是一个全球性的问题。由于糖尿病在世界各地都达到了流行的程度，支持性统计数据令人震惊。所有糖尿病患者中有 80%生活在发展中国家。在这篇综述中，我们描述了纤溶酶原激活物抑制剂-1（PAI-1）在肥胖和糖尿病病理中的作用及其作为治疗靶点的潜力。PAI-1 是组织型纤溶酶原激活物（tPA）和尿激酶（uPA）的快速作用和特异性抑制剂，tPA 和 uPA 是纤溶酶原的激活剂，因此也是纤维蛋白溶解的激活剂。在肥胖和糖尿病中，它与血栓形成的发生率增加有关。然而，PAI-1 也参与了其他参与止血的蛋白质的调节。这些分子包括转化生长因子β（TGF-β）、肿瘤坏死因子α（TNF-α）、血管紧张素 II 和白细胞介素 6（IL-6），所有这些分子在各种细胞类型中都能上调 PAI-1，或者可以被 PAI-1 上调。因此，PAI-1 在导致 2 型糖尿病的胰岛素抵抗综合征中起着关键作用，并且与糖尿病肾病、动脉粥样硬化性心血管疾病等的发生风险增加等副作用有关。因此，使 PAI-1 失活或增加其清除率可以减轻肥胖和糖尿病的负担。
