Investigations of beta cell dysfunction and death in type 2 diabetes

糖尿病是一种影响全球1亿人的疾病，预计这一数字在未来20年内将翻一番。这种疾病的特点是血糖水平高，长时间会影响肾脏和眼睛的功能，并导致心脏病发作和中风。糖尿病的一个主要因素是胰腺无法分泌胰岛素，胰岛素是一种负责将血糖水平保持在正常范围内的激素。胰腺不能分泌足够的胰岛素的原因尚不清楚。然而，众所周知，遗传和环境因素都是造成这种现象的原因。这项研究的目的是确定糖尿病动物模型DBA-2J小鼠胰岛素分泌减少的生化和遗传原因。具体地说，我们将研究长期增加的糖和脂肪对胰腺胰岛素产生细胞功能的影响，以确定导致胰岛素分泌减少的生化途径。与此同时，我们将研究DBA-2J小鼠中导致胰岛素分泌减少和胰腺细胞死亡的一个或多个基因。这将为可能导致人类糖尿病的基因提供线索。该项目将在细胞和基因水平上提供有关胰岛素分泌减少原因的关键信息，并将有助于更好地了解糖尿病的病因。

Diabetes is a disease that affects 100 million people worldwide and this number is expected to double in the next twenty years. This disease is characterised by high blood sugar levels which over prolonged periods of time can affect the function of the kidneys and eyes as well as causing heart attacks and strokes. A main contributing factor to diabetes is the inability of the pancreas to secrete insulin, the hormone that is responsible for keeping blood sugar levels in the normal range. The reason for this inability of the pancreas to secrete enough insulin is not known. It is known however, that both genetic and environmetal factors are responsible. The aim of this investigation is to determine the biochemical and genetic reason for decreased insulin secretion from an animal model of diabetes called DBA-2J mouse. Specifically we will be studying the effects of long-term increased sugar and fat on the function of the insulin producing cells of the pancreas, in order to identify the biochemical pathway responsible for reduced insulin secretion. In parallel we will be investigating the gene or genes in DBA-2J mice that are responsible for decreased insulin secretion and pancreatic cell death. This will provide clues as to the genes that may be responsible for diabetes in humans. This project will provide crucial information on the cause of reduced insulin secretion both at the cellular and genetic level, and will lead to a better understanding of the cause of diabetes.