The role fructose-1,6-bisphosphatase on the regulation of hepatic gluconeogenesis

2型糖尿病或成人糖尿病是一种以高血糖为特征的疾病，会对肾脏、眼睛和血液循环造成损害，许多患者死于心脏病发作或中风。澳大利亚的糖尿病患病率正在增加，医疗预算的很大一部分用于照顾糖尿病患者。确定究竟是什么原因导致血糖水平上升，在治疗这种疾病方面至关重要。众所周知，肝脏产生和释放的糖是糖尿病患者高血糖水平的重要因素。导致这一现象的主要生化途径被称为糖异生，这是一种复杂的酶的排列，将氨基酸和脂肪转化为糖。尽管已知糖尿病患者体内这一途径过度活跃，但其确切原因尚不清楚。这项提议的目的是培育一种转基因小鼠，这种转基因小鼠的肝糖产量因糖异生增加而增加，并研究其对血糖水平的影响。此外，将通过给转基因小鼠注射胰岛素来了解这一途径的调节，胰岛素是一种抑制糖异生的激素。胰岛素的作用机制将通过测量调节糖异生的关键酶来确定。这笔赠款的意义是确定可能用于开发新药或基因疗法的地点，这些药物或基因疗法将导致肝脏产生的糖减少。这将有助于更好地控制血糖水平，减缓甚至预防糖尿病并发症的发生。

Type 2 or adult onset diabetes is a disease characterised by high blood sugar that causes damage to the kidneys, eyes and to the circulation and many patients die from heart attack or stroke. There is an increase in the prevalence of diabetes in Australia and a substantial portion of the health budget is utilised by caring for people with diabetes. Determining what exactly causes the increase in blood sugar levels is critical in the treatment of the disease. It is known that the sugar produced and released by the liver is an important contributor to the high blood sugar levels found in patients with diabetes. The main biochemical pathway responsible for this is called gluconeogenesis, a complex arrangement of enzymes, which convert amino acids and fat into sugar. Although it is known that this pathway is overactive in patients with diabetes, the exact reason for this is not clearly understood. The aim of this proposal is to produce a transgenic mouse that has an increase in liver sugar production as a result of an increase in gluconeogenesis, and to study its effects on blood sugar levels. Furthermore, studies will be performed to understand the regulation of this pathway by infusing the transgenic mice with insulin, the hormone that inhibits gluconeogenesis. The mechanism of action of insulin will be determined by the measurement of key enzymes that regulate gluconeogenesis. The significance of this grant is to identify possible sites for the development of new drugs or gene therapy that will lead to a decrease in the production of sugar by the liver. This will lead to better control of blood sugar levels and slow down or even prevent the onset of diabetes complications.