(64f) A Possible Role for Uncoupling Protein 2 in the Development of Insulin Resistance

Type 2 Diabetes is becoming a major health concern throughout the world. Recent clinical evidence points to restoring overall insulin sensitivity as the major objective in the management of Type 2 Diabetes. Current research indicates Uncoupling Protein 2 may play a role in the development of insulin resistance and the onset of Type 2 Diabetes. UCP2 over expression has been linked to increases in reactive oxygen species concentration. The presence of UCP2 has been linked to the ability of the cell to perform insulin-stimulated uptake of glucose. Tumor Necrosis Factor α has also been linked to increases in ROS concentration and the insulin sensitivity of the cell. This evidence suggests a link between UCP2, ROS, TNF-α, and insulin resistance. The overall objective of our research is to establish the relationship between UCP2 and ROS in the context of insulin resistance in 3T3-L1 adipocytes with the specific aim of determining the effect of UCP2 expression on ROS concentration. To date we have succeeded in cloning the UCP2 gene into an inducible plasmid, pRev-TRE, inducible by the addition of Doxycycline. The development of a lentiviral vector, able to integrate the pRev-TRE UCP2 plasmid into the genome of 3T3-L1 adipocytes, is currently underway. Our future work will include experiments quantifying the concentration of ROS in the presence of various UCP2 expression conditions including: baseline physiological, blank, and over expression.