Potential Role of SHP-1 in Angiotensin II-induced Insulin Resistance

There are many contributing factors to the development of Type II diabetes mellitus (DM2), including both genetics and lifestyle factors, such as poor diet and lack of exercise. On the molecular level Diabetes Mellitus Type 2 (DM2) is characterized by the development of insulin resistance, in which cells do not correctly respond to the effects of insulin. The molecular mechanisms that are responsible for the development of insulin resistance are not well understood and are of significant importance, considering the high prevalence of DM2 in our population. It is known from the current literature that the proteins AKT, PI3Kinase, JAK2, SHP-1 and PTEN are involved in the pathology of DM2, but there is much to be learned yet. This thesis investigated the role of the intracellular protein SHP-1 to determine if Angiotensin II utilized it in the molecular mechanisms of insulin resistance. I used sample tissues from canine kidney cortexes that were treated with various concentrations of insulin and Angiotensin II. These samples were generated by our collaborator at the Medical College of Georgia. We hypothesized that an increase in SHP-1 activity would result in decreased AKT activation, leading to insulin resistance and eventually DM2.