Integrin-Mediated Regulation of Insulin Sensitivity
An increase in blood glucose causes secretion of insulin. Insulin reduces blood glucose level by promoting glucose uptake by skeletal muscles and other tissues. Diabetic patients are resistant to the effects of insulin leading to high blood glucose levels. The objective of this study is to better understand how insulin resistance develops. We have found an increase in expression of a particular protein, MFGE8, in obese and insulin-resistant mice that regulates the ability of the body to respond to insulin. In the studies, we will figure out how this protein works with the goal of eventually targeting it as a new treatment for insulin resistance.
Insulin binding of its receptor leads to receptor activation which ultimately triggers glucose uptake. Over time, activation of the insulin receptor must be turned off to prevent uncontrolled glucose uptake. Based on our preliminary data, we hypothesize that MFGE8 binding of the β5 Integrin terminates insulin signaling, thereby providing an ‘off switch’ that regulate insulin mediated glucose uptake under homoeostatic condition. Testing this hypothesis will help us understand the complex regulation of insulin receptor deactivation, an area of research which is relatively less explored. Moreover, we will determine the therapeutic potential of inhibiting this pathway in mouse model of diabetes.