Submitted March 22, 2007
Accepted August 10, 2007
Insulin-like growth factor-1 regulates platelet activation through PI 3-K
isoform
Soochong Kim, Analia Garcia, Shaun P Jackson, and Satya P Kunapuli*
Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, United States
Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA, United States
Australian Center for Blood Diseases, Monash University, Melbourne, Victoria, Australia
Department of Physiology, Temple University School of Medicine, Philadelphia, PA, United States
* Corresponding author; email: spk{at}temple.edu.
Platelets release IGF-1 from 
-granules upon activation. We have investigated the regulation of IGF-1 in Gi-dependent pathways leading to Akt activation and the role of IGF-1 in platelet activation. IGF-1 alone failed to induce platelet aggregation, but IGF-1 potentiated 2-MeSADP-induced platelet aggregation in a concentration-dependent manner. IGF-1 triggered platelet aggregation in combination with selective P2Y1 receptor activation. IGF-1 also caused platelet aggregation without shape change when combined with selective Gz stimulation by epinephrine suggesting the role of IGF-1 in platelet aggregation by supplementing Gi pathways. Potentiating effect of IGF-1 was not affected by intracellular calcium chelation. Importantly, IGF-1 was unable to potentiate platelet aggregation by phosphatidylinositol 3-kinase (PI3-K) inhibitor wortmannin suggesting a critical regulation by PI3-K. Moreover, the potentiating effect of IGF-1 was abolished by the presence of PI3-K p110 inhibitor PIK-75. Stimulation of platelets with IGF-1 resulted in phosphorylation of Akt, a downstream effector of PI3-K, which was completely inhibited by wortmannin. IGF-1-induced Akt phosphorylation was abolished by PIK-75 suggesting the contribution of PI3-K p110 for activation of Akt by IGF-1. These results demonstrate that IGF-1 plays a role in potentiating platelet aggregation by complementing Gi, but not Gq, signaling pathways via PI3-K p110.
