Background: Diabetes mellitus is one of the common causes for activation of platelet. Inflammation-induced abnormal platelet function contributes to chronic complications. Aim: Ras-related C3 botulinum toxin substrate 1 (Rac1) a 21kD G-protein, has been shown to regulate a variety of platelet functions; we predicted that Rac1 could regulate platelet release of CXCL4 and CCL5, which leads to macrovascular and microvascular complications under diabetes mellitus. Method: 150 confirmed diabetic patients which they visit Layla Qasim health center for diabetes and 50 healthy individuals were included in this study. The serum CXCL4 and CCL5 in diabetic patients and healthy volunteer were measured. Swiss albino male mice were pretreated with 5 mg/kg of a specific Rac1 inhibitor NSC23766 and injected with (45 mg/kg body wt.) streptozotocin, twice for five days. Rac1 activity in the platelet was measured using pulldown assay and western blot method. Moreover, the concentration of serum chemokines were assayed using ELISA and histology score for kidney, liver, pancreas and lung were examined. Results: CXCL4 and CCL5 were significantly higher in diabetic patients compared to healthy individuals. Our results showed that Diabetes mellitus was induced in mice by streptozotocin. GTP-Rac1 was induced in diabetic mice and pretreatment with NSC23766 was significantly lower compared to vehicle group. In addition, CXCL4 and CCL5 were markedly higher in diabetic mice when compared to the sham group P-value <0.05. Conclusion: Our study reveals that Rac1 has a critical role in platelet chemokines secretion due to diabetes-induced inflammation in the organs and targeting Rac1 could be an innovative treatment to control inflammation in diabetic individual. 

TBA