The role of FBPase in beta cell dysfunction

2型糖尿病是由多种基因缺陷引起的，导致高血糖水平。这些高血糖水平主要是由于胰岛素浓度的下降，胰岛素是一种由胰腺产生的激素。最近的一些研究旨在确定哪些基因在模拟糖尿病的条件下受到调控。在这些条件下，有一个基因的表达水平发生了变化，那就是一种名为果糖-1，6-二磷酸酶(FBPase)的酶。这种酶参与糖的新陈代谢，通常在胰腺中以无法检测到的水平表达，但当血糖水平较高时，胰腺中的FBPase数量会显著增加。我们推测，在糖尿病状态下，这种FBPase的增加可能有助于胰腺胰岛素分泌的减少。因此，这项建议的目的是研究我们已经改造成特定在胰腺表达增加的FBPase的小鼠，以确定这是否会导致胰岛素释放减少和糖尿病。如果是这样的话，FBPase可能会被用于开发可以改善糖尿病患者血糖水平控制的药物。

Type 2 diabetes is caused by multiple genetic defects, resulting in high blood sugar levels. These high sugar levels are primarily due to a decrease in the concentration of insulin, a hormone produced by the pancreas. A number of recent studies have aimed to identify which genes are regulated under conditions that mimic diabetes. One gene shown to have altered expression levels under these conditions is an enzyme called fructose-1,6-bisphosphatase (or FBPase). This enzyme is involved in the metabolism of sugar and is usually expressed at undetectable levels in the pancreas, but when blood sugar levels are high, the amount of FBPase in the pancreas increases considerably. We hypothesise that this increase in FBPase may contribute to the decrease in insulin secretion by the pancreas, seen in the diabetic state. The aim of this proposal therefore is to study mice that we have modified to express increased FBPase specifically in the pancreas, in order to determine whether this will lead to a decrease in insulin release and to diabetes. If this is the case, then FBPase could be targeted for the development of drugs that would improve the control of blood sugar levels in diabetes.