Investigation of the genetic basis of insulin hypersecretion in a mouse model of pancreatic islet failure

2型糖尿病是一种慢性疾病，与失明、肾衰竭、心脏病发作和中风有关，这些都是继发于高血糖水平的。因此，确定2型糖尿病患者高血糖水平的原因将有助于更好地管理该疾病，并减轻公共卫生系统的经济负担。2型糖尿病患者的高血糖是由于身体不能分泌足够的胰岛素引起的。胰岛素是降低血糖水平的主要激素，由胰腺产生。2型糖尿病患者胰岛素分泌减少的原因尚不清楚。矛盾的是，一些患糖尿病风险增加的人（如肥胖或有糖尿病家族史的人）分泌的胰岛素比正常人多。目前还不清楚为什么会这样，但一些研究表明，在这种情况下减少胰岛素分泌可以保护胰腺并保持其分泌适量胰岛素的能力。DBA-2是一种像人类2型糖尿病患者一样的小鼠品系，它的胰腺也可能无法分泌适量的胰岛素，在这种情况下就会患上糖尿病。此外，我们的实验室已经有证据表明，与有患糖尿病风险的人一样，DBA-2小鼠在患糖尿病之前实际上分泌了更多的胰岛素。胰岛素分泌增加的原因是否与最终分泌减少有关尚不清楚。本研究的目的是确定导致DBA-2小鼠胰岛素分泌增加的基因。此外，将生产只含有该基因的转基因动物，以确定其对胰岛素分泌的影响。如果这种基因的鉴定与胰腺分泌足够胰岛素的最终失败有关，那么它将为药物治疗提供一个目标，以纠正胰岛素水平，从而降低血糖水平。

Type 2 diabetes is a chronic disease that is associated with blindness, kidney failure, heart attacks and stroke and these are secondary to high blood sugar levels. Thus, determining the cause of high blood sugar levels in type 2 diabetes will lead to better management of the disease and ease the financial burden on the public health system. High blood sugar in type 2 diabetes results from the inability of the body to secrete enough insulin. Insulin is the main hormone that lowers blood sugar levels and is produced by the pancreas. The reason for reduced insulin secretion in type 2 diabetes is not known. Paradoxically, it has been shown that some people who are at an increased risk of developing diabetes (eg people with obesity or a family history of diabetes) secrete more insulin than normal. It is not clear why this is, but a few studies have suggested that reducing insulin secretion in these circumstances can protect the pancreas and preserve its ability to secrete the appropriate amount of insulin. The DBA-2 is a mouse strain that like humans with type 2 diabetes, its pancreas can also fail to secrete the appropriate amount of insulin and under these circumstances becomes diabetic. Furthermore our laboratory has generated evidence that shows that like people who are at risk of diabetes, DBA-2 mice in fact secrete more insulin prior to becoming diabetic. Whether the cause of this increased insulin secretion is linked to the eventual reduction of secretion is not known. The aim of this study is to identify the gene that causes increased insulin secretion in the DBA-2 mouse. Furthermore, genetically manipulated animals will be produced that contain only this gene to determine its effect on insulin secretion. Should the identification of this gene be related to the eventual failure of the pancreas to secrete enough insulin, then it would provide a target for drug therapy to correct insulin levels and therefore reduce blood sugar levels.