Question

A group of researchers is studying an mTOR inhibitor called Torben. What effects (1, = or 1) should they expect on the following measures in muscle of fed dogs injected with Torben compared to those injected with vehicle only? For each effect, describe the cause (7 words).

a) S6 kinase activity

b) The researchers found a decrease in glucose uptake by muscle. Explain how an mTOR inhibitor could cause this decrease

c) Knowing that glucose absorption from the diet was the same on both treatments, where would the extra glucose go that was not being used by muscle during Torben administration? Name the organ/tissue and the end-product of glucose use.

Answer 1

a) Decreases. S6 kinase is an effector kinase of mTOR for the activation of protein synthesis. mTOR phosphorylates S6K on its hydrophobic motif site Thr 389 leading to it's phosphorylation and activation by PDK1.

b) mTOR pathway is activated by the presence of insulin. When body has elevated glucose levels, pancreatic cells produce more insulin which in turn binds to the insulin receptors of skeletal muscle cells to uptake more glucose. When insulin binds to insulin receptor, mTOR pathway gets activated , increased GLUT production and translocation to the membrane leading to increased glucose uptake by muscle cells.

When an mTOR inhibitor is present, glucose uptake decreases since mTOR pathway isn't activated leading to insulin resistance of the cell.

c) mTOR inhibition in muscle cells will take lead to failure in glucose uptake and elevated levels of glucose and insulin in the blood. It leads to hyperactivated mTOR activity in Liver and adipose tissue. The production and translocation of GLUT4 increases in these cells there by leading to more uptake of glucose. in adipocytes it leads to the produxprod and activation glycogen synthase enzymes and convertion of glucose in to glycogen and it's accumulation.