Regulation of glucose homeostasis and insulin signalling by Grb10 and Grb14.

点击翻译按钮获取中文摘要

The hormone insulin is a critical regulator of blood glucose levels. Defective insulin action, also known as insulin resistance, underlies the development of Type 2 Diabetes, which is major health problem worldwide. Understanding how insulin action is regulated may lead to new treatments for this disease. Insulin mediates its effects by binding to a receptor on the cell surface that transmits signals to the interior of the cell. Depending on the cell type, these signals can instruct the cells to take up glucose from the bloodstream (muscle and fat) or decrease glucose production (liver). We have identified a new regulator of insulin signalling in cells, a protein termed Grb14. This was accomplished by generating mice in which the Grb14 gene was removed, so that the animals no longer produced Grb14. These animals responded better to insulin, indicating that Grb14 normally inhibits insulin action. However, it is likely that another closely related protein, Grb10, functions alongside Grb14 to regulate insulin signalling. Therefore, we will use mice in which the Grb10 and Grb14 genes have been removed, singly and in combination, to define the roles of these two proteins in regulating blood glucose levels and insulin signals inside the cell. We will also use cells isolated from the mice to analyse the molecular events underlying the effects of Grb10 and Grb14 on insulin signalling. The significance of these studies is that defining the functional role and mode of action of Grb10 and Grb14 may lead to novel therapeutic approaches aimed at blocking their function. Such approaches could be used to overcome the insulin resistance associated with Type 2 Diabetes.