Molecular mechanisms of impaired glucose transport in insulin resistance

2型糖尿病是全球主要的健康挑战之一，确诊人数超过4亿。胰岛素抵抗是一种激素胰岛素不再能够有效控制血糖水平的情况，是2型糖尿病发展的主要危险因素。此外，胰岛素抵抗还与许多其他慢性疾病有关，包括心血管疾病、某些癌症和神经退行性疾病。因此，克服胰岛素抵抗的治疗将为2型糖尿病提供新的治疗选择，并有助于减轻其他胰岛素抵抗相关疾病的负担。胰岛素降低血糖水平，部分是通过增加葡萄糖转运到脂肪和肌肉组织，在那里它可以被利用或储存。胰岛素抵抗的潜在原因之一是葡萄糖从血液转运到这些组织的缺陷。脂肪和肌肉细胞内的过程是胰岛素增加健康个体葡萄糖运输所必需的。然而，目前尚不清楚这些过程是如何或哪些在胰岛素抵抗中受损的。我的奖学金提案的目的是通过领导研究来确定葡萄糖向脂肪和肌肉组织的运输在胰岛素抵抗中被破坏的原因，从而解决这一知识空白。我工作的长期目标是利用这些信息找出对抗胰岛素抵抗的合理方法。改善或恢复葡萄糖转运到脂肪和肌肉组织以治疗胰岛素抵抗将对人类健康产生两大影响。首先，这将解决目前2型糖尿病治疗方案的空白，因为目前没有直接针对葡萄糖转运的药物。其次，由于胰岛素抵抗现在与其他几种慢性疾病有关，克服胰岛素抵抗的新疗法可能具有比2型糖尿病更重要的意义。

Type 2 diabetes represents one of the major worldwide health challenges, with more than 400 million people diagnosed. Insulin resistance, a condition where the hormone insulin is no longer able to efficiently control blood glucose levels, is a primary risk factor for the development of type 2 diabetes. In addition, insulin resistance is also linked to a number of other chronic diseases including cardiovascular disease, some cancers and neurodegenerative disorders. Therefore, treatments to overcome insulin resistance would provide new therapeutic options for type 2 diabetes and could help reduce the burden of other insulin-resistance associated diseases.Insulin lowers blood glucose levels, in part, by increasing glucose transport into fat and muscle tissue where it can be utilised or stored. One of the underlying causes of insulin resistance is a defect in the transport of glucose from the blood into these tissues. The processes within fat and muscle cells that are required for insulin to increase glucose transport in healthy individuals is well known. However, is not known how or which of these processes are impaired in insulin resistance. The aim of my fellowship proposal is to address this gap in knowledge by leading studies to identify the reason that the transport of glucose into fat and muscle tissue is disrupted in insulin resistance. The longer-term goal of my work is to use this information to identify rational ways to combat insulin resistance. Improving or restoring glucose transport into fat and muscle tissues to treat insulin resistance will have two major implications for human health. Firstly, this will address a current gap in treatment options for type 2 diabetes since there are no current medications that directly target glucose transport. Secondly, since insulin resistance is now linked to a several other chronic diseases, new therapies to overcome insulin resistance may have significant implications beyond type 2 diabetes.