Ranolazine reduced palmitic acid-induced insulin resistance in cardiomyocytes by normalizing Ca2+/CaMKII and was linked to lower hyperglycemia risk in coronary artery disease patients.
Does ranolazine improve insulin resistance and reduce the risk of hyperglycemia in coronary artery disease patients and diabetic cardiomyocytes?
Ranolazine may offer metabolic benefits by ameliorating insulin resistance and reducing the risk of hyperglycemia in patients with coronary artery disease.
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Abstract Background and Aims Diabetes mellitus (DM) significantly increases the risk of cardiovascular disease (CVD), the leading cause of death among DM patients. The pathophysiology of diabetic cardiac injury involves insulin resistance, substrate utilization imbalances, and calcium dyshomeostasis. In diabetic cardiomyocytes, excess fatty acids impair insulin signaling, reduce GLUT4 translocation, and increase lipid accumulation, leading to contractile dysfunction. Current study we investigated the therapeutic potential of Ranolazine (RAN), a second-line treatment for stable angina, in improving insulin resistance in diabetic cardiomyocytes. Methods In the in vitro model, we used the HL-1 cardiomyocyte cell line for experimental design and treatment with ranolazine. In the population-based cohort study, we used the TriNetX Global Collaborative Network cohort database to demonstrate the beneficial effect on glucose level by ranolazine therapy among coronary artery disease patients. Results Using the HL-1 cardiomyocyte cell line, we demonstrated that RAN treatment could normalize Ca2+/calmodulin kinase-II (CaMKII) activity, reduce lipid accumulation, and thus enhance GLUT4 exocytosis. Our results showed that RAN could significantly decrease palmitic acid-induced insulin resistance, evident by increased phosphorylation of AKT and GSK-3β. Additionally, RAN treatment also restored metabolic flexibility by upregulating acetyl-CoA carboxylase (ACC) and maintaining CD36 expression. Intracellular calcium measurements indicated that RAN could effectively mitigate calcium overload in diabetic cardiomyocytes. Furthermore, RAN promoted GLUT4 translocation to the plasma membrane and improved glucose uptake. In the population-based cohort study, our results indicated that ranolazine use was associated with a reduced risk of hyperglycemia after accounting for all measured confounders. Conclusions These findings suggest that RAN modulates key molecular pathways involved in diabetic cardiomyopathy.Concept of our RAN mechanism study Less hyperglycemia for RAN (blue) use
Vairaperumal et al. (Sat,) reported a other. Ranolazine reduced palmitic acid-induced insulin resistance in cardiomyocytes by normalizing Ca2+/CaMKII and was linked to lower hyperglycemia risk in coronary artery disease patients.
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