Investigation of transgenic mouse models of Type 2 diabetes

2型糖尿病是一种以高血糖为特征的常见疾病，困扰着70万澳大利亚人。它会导致失明、肾衰竭，并增加心脏病发作和中风的风险。尽管多年来进行了深入研究，但在这种情况下血糖升高的原因尚未完全了解。几种异常可能导致高血糖，不同的研究人员提出了不同的缺陷作为最初的原因。已经证明很难解开该综合征演变过程中的事件顺序，因为高葡萄糖可引起胰岛素抵抗和胰岛素分泌缺陷，这两者都可导致高血糖。研究特定缺陷后果的一种方法是对它们进行基因工程。该项目的目标是：1。使老鼠肌肉中储存葡萄糖的能力降低。2.测试肌肉中糖原（淀粉）制造缺陷的代谢后果。3.研究葡萄糖储存缺陷与导致葡萄糖供应过剩的缺陷相结合的影响。4.研究对具有β细胞（胰岛素制造细胞）失败遗传倾向的小鼠的影响，所述β细胞失败是肌肉葡萄糖储存缺陷和葡萄糖过度产生的结果。这项资助的成功完成将大大提高我们对2型糖尿病血糖升高的理解。

Type 2 diabetes is a common condition characterised by high blood glucose, that afflicts 700,000 Australians. It causes blindness, kidney failure and an increased risk of heart attack and stroke. despite intensive study over many years, the reasons for the elevated blood glucose in this condition are not fully understood. Several abnormalities can contribute to the high glucose and different researchers have proposed different defects as the initial cause. It has proven difficult to unravel the sequence of events in the evolution of the syndrome because high glucose can cause insulin resistance and a defect in insulin secretion, both of which can lead to high blood glucose. One approach to study the consequences of specific defects is to genetically engineer them. The aims of this project are to: 1. make a mouse with reduced ability to store glucose in muscle. 2. test the metabolic consequences of a defect in the manufacture of glycogen (starch) in muscle. 3. study the effects of combining a defect in glucose storage with one that results in an oversupply of glucose. 4. study the effects on a mouse with a genetic predisposition for failure of beta cells (insulin making cells) of a defect in muscle glucose storage and over production of glucose. A successful completion of this grant will greatly enhance our understanding of how blood glucose is increased in Type 2 diabetes.