| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2003: ¥2,000,000 (Direct Cost: ¥2,000,000)
|
|---|
| Research Abstract |
Insulin stimulates glucose uptake in skeletal muscle and adipose tissues primarily through regulation of the subcellular distribution of the glucose transporter 4 (GLUT4). In response to insulin, a fraction of GLUT4 present in intracellular membranes is redistributed to the plasma membrane, resulting in an increase of GLUT4 on the cell surface and enhanced glucose uptake. This effect of insulin is important in maintaining glucose homeostasis in humans, and impaired insulin action can contribute to the pathogenesis of type 2 diabetes. We focused to molecular motors that took part in the GLUT4 translocation. Here, we show that some myosin and dynein motors expressed in culture adipocytes. A myosin motor Myo1c have roles not only to transport vesicles containing GLUT4 but also to convey IKK complex, resulting inhibition of insulin signaling. This is the first report that signal molecules were transported by a molecular motor. Then, we revealed that dynein motor have a role on GLUT4 recycling in adipocytes. Moreover, CLIP-170 was identified. This protein exists only on the plus end of microtubules. Interestingly, CLIP-170 mediates GLUT4 transport between actin and microtubule. Furthermore, this protein can hold vesicles containing GLUT4 in insulin and actin dependent manner. Unfortunately, we could not find any kinesin motors in adipocytes.
These findings have a potential to reveal a missing link between insulin signaling molecules and GLUT4 translocation.
|
