Insulin treatment of fat and muscle cells causes a rapid increase in glucose transport. The basis for this effect is an increase of glucose transporters of the GLUT4 type at the cell surface. This translocation of GLUT4 is achieved by modification of AS160 (Akt substrate of 160-kDa) which has a GTPase activating protein (GAP) domain for members of the Rab G protein family. AS160 is phosphorylated by the insulin-activated protein kinase Akt, Evidence indicates that phosphorylation of AS160 inhibits its GAP activity, thereby elevating the GTP form of Rab(s) required for GLUT4 translocation, so that translocation is triggered.
Dartmouth researchers have now found that there is a small subset of select Rab proteins, namely Rab 2A, 8A, 10 and 14, which serve as substrates for the GAP domain of AS160. The location of these select Rab proteins on GLUT4 vesicles is indicative of the involvement of one or more in GLUT4 translocation. Thus, agents that inhibit the gtpase activity of AS160 toward GTP-bound Rab 2A, 8A, 10 or 14 proteins can now be identified. These agents are expected to stimulate the delivery of GLUT4 to the plasma membrane,and so have the potential to be agents that lower the blood glucose level.
This technology is claimed in the published United States Patent Application No. 11/817,819. We are seeking an industrial partner interested in its commercialization. (Ref: J306)
Last Updated: 7/24/12