Grant: Operating Grant

When obese people develop type 2 diabetes, it could be because the cells that produce insulin make less insulin, and their body cannot use the insulin it makes as effectively, a condition called insulin resistance. Obesity puts stress on the endoplasmic reticulum (ER), a compartment of all the cells in our body. Normally when the ER is stressed, it protects the cells by elaborating a process called the unfolded protein response (UPR). In obese mice, the UPR is excessively activated. This makes the cells less sensitive to insulin, thereby it is harder for the body to lower blood glucose levels. We have discovered that a protein called Nck is involved in the regulation of the UPR. Recently, we have provided strong evidence that Nck is important in the development of insulin resistance in obese mice through its role in regulating the UPR. More importantly, we have identified Nck as a negative regulator of insulin action in liver. Therefore, during the next 5 years, we will determine how Nck counteracts insulin action in liver. By learning more about Nck related to the UPR and insulin signaling, we will be able to find new ways of treating or preventing type 2 diabetes.