Platelet Function in Patients with Diabetes Mellitus: From a Theoretical to a Practical Perspective

Figure 1

Pathways involved in platelet hyperreactivity in DM patients and therapeutic targets. AGE: advanced glycation end products, RAGE: AGE receptors, PKA/B/C: protein kinase A/B/C, MAPK: p38 mitogen-activated protein kinase, TK: tyrosine kinase, NO: nitric oxide, GC: guanylate cyclase, PAR-1 TR: protease activated receptor; thrombin receptor, PI-3: phosphoinositol-3 kinase TRA: thrombin receptor antagonist, TPα: thromboxane receptor, TPRA: thromboxane receptor antagonist, and ASA: acetylsalicylic acid (aspirin). Increased levels of cAMP lead to platelet inhibition through cAMP-dependent protein kinase (PKA) which inhibits signaling though the mitogen-activated protein kinases pathway, receptor activation, thromboxane A2 formation, and activation of key enzymes such as protein kinase C. The prostaglandin, P2Y, P2X, TR, and TP are all seven transmembrane G-protein associated receptors. The TR and TP on the right present novel drug targets; their intracellular effectors are omitted for clarity. Antiplatelet drugs are shown in red.