Early Up-Regulation of Multiple Signaling Pathways in Type I Diabetic Cardiomyopathy

The present study seeked to test the hypothesis that diabetes, characterized by overactivity of the local Rennin-angiotensin System (RAS), leads to signals enhancement and diversification at branching points and thus permits combinatorial interactions between multiple pathways. The streptozotocin (STZ) rat model of type I-diabetes were investigated and confirmed earlier studies that hyperglycemia activates RAS. The pathways discussed in the present study were analyzed using Western blot analysis to investigate the protein density for each pathway. Mitogen-activated Protein Kinase (MAPK) Cascades, showed altered activation in the heart of STZ-diabetic animals. The present study shows, for the first time, that the phosphorylation of Akt (protein kinase B, PKB) is significantly increased as early as 14 days following induction of type-I diabetes. Since Akt plays a critical role in controlling the balance between survival and apoptosis, further research is urgently required for understanding the molecular basis of Akt activity dysregulation which may leads to new therapeutic discovery.