Advantages of Phosphodiesterase Type 5 Inhibitors in the Management of Glucose Metabolism Disorders: A Clinical and Translational Issue

Figure 1

Schematic representation of PDE5i action in insulin-related pathways. PKG activated by cGMP exerts positive effects on IRS downstream effectors. The phosphorylation of PKB/AKT induces the translocation of GLUT4 vesicles on plasma membrane, favoring glucose uptake and activation of downstream signaling involved in protein synthesis, cell growth, and differentiation. The balance between cGMP synthesis (induced by the interaction of NO with sGC) and cGMP hydrolysis (by PDE5) regulates cGMP levels. The action of the PDE5i promotes the accumulation of cGMP. IR: insulin receptor; NO: nitric oxide; sGC: guanylyl cyclase; PDE5: phosphodiesterase type 5; GMP: guanosine monophosphate; cGMP: cyclic guanosine monophosphate; IRS: insulin receptor substrate; PI3K: phosphatidilinositol 3-kinase; PKB/AKT: protein kinase B/AKT; and mTOR: mammalian target of ramapycin.