Diabetes Paper

Animal Model of Diabetes Type 2

There are two types of diabetes: Type 1 and Type 2. Type 1 diabetes is mostly diagnosed in juvenile, while type 2 is mostly diagnosed after the age of 35. Type 1 diabetes is primarily caused by destruction of pancreas which is responsible for producing insulin. However, in type 2 diabetes, insulin resistance is seen in the body, i.e., enough insulin is produced by the body but its activity (conversion of glucose to glycogen) is blocked. Thus, the end result of both types of diabetes is similar: increase level of blood glucose. Also, the cellular mechanism through which type 2 diabetes occurs is poorly understood, this type is found among 85-90% of diabetic patients. Research has shown that the AKT and Hdac4 are one of the major downstream targets of insulin signaling pathway. One of the roles of Hdac4 is acetylation/deacetylation of FoxO genes, which are responsible for gluconeogenesis.

We plan on looking at the AKT pathway: insulin signals the Akt which phosphorylates Hdac4 (inactivate Hdac4) and leads to glycogen synthesis. However, when this signaling pathway is impaired glycogen synthesis process is disturbed. There are three kinds of AKT distributed in the body: AKT 1, 2, and 3. We specifically plan to look at AKT2 which is predominantly present in liver. As mentioned above, one of the novel targets of AKT is Hdac4 which is responsible for acetylation/deacetylation of FoxO genes. These genes when deacetylated are responsible for gluconeogenesis. The animal models used in past research include: mouse, rat, sheep, fruit flies, monkeys, and horses. The model that best fits our research would be the mouse model. This is primarily because of the pathway we are looking at. Only rats and mice have AKT 1 and AKT2 genes which are also present in humans. Rats would not be the best model since they are higher in hierarchy. As a result, they would cost more than mice. This research could be successfully carried out using a lower hierarchy animal such as mice.