Figure 2. Enhanced mTOR signaling in diabetic glomerulopathy.
Increased glucose uptake into diabetic mesangial cells (and perhaps other renal cells) leads to reduced AMPK activation and reduced association of TSC1 and TSC2, allowing for Rheb activation of mTOR. Increased glycolysis and activation of GAPDH can lead directly to Rheb activation of mTOR by reducing Rheb binding to GAPDH.
AMPK: AMP kinase; S6K: S6 kinase; TSC: Tuberous sclerosis complex.