Fig. 2

Effects of insulin, rapamycin, and wortmannin on key proteins and their interactions. Insulin was lowered to 10% of its baseline level for the initial 40 min of the simulation, and subsequently returned to baseline level. Simulations are conducted for control, acute and chronic administration of rapamycin, chronic administration of rapamycin with wortmannin. The inhibition of PRAS40 of mTORC1 is represented in the left panels but not the right ones. Included also are experimental time-course data for mTORC1_pS2448 and p70S6K_pT389 [11]; points and dotted error bars represent mean and SEM. Model predicts that PRAS40 substantially lowers mTORC1 level under low insulin conditions. That effect is the most prominent under chronic administration of rapamycin and wortmannin