The Effect Of ERK1/2 Inhibitor On Cardiomyocyte Hypertrophy Induced By High Glucose And Insulin In Cultured Neonatal Rat Cardiomyocytes

Objective:Hyperglycemia and hyperinsulinemia is a main complication of type 2 diabetes mellitus.In recent years,it has been proved that type 2 diabetes mellitus has effects on the development of cardiomyocyte hypertrophy.It plays a critical role in type 2 diabetes complicating cardiac hypertrophy.Hyperglycemia and hyperinsulinemia relates to the expression of cardiatrophin-1(CT-1).CT-1 displays its biological functions via several signal conduct pathways,in which extracellular-signal regulated protein kinase 1/2(ERK1/2)pathway is an important one.However,it is still unclear what effects it plays on cardiomyocyte hypertrophy induced by CT-1.In the present study,ERK1/2 inhibitor was used to determine whether ERK1/2 pathway participates the cardiomyocyte hypertrophy induced by CT-1.Methods:Cardiomyocytes of neonatal Wistar rat were cultured in vitro.Then the cardiomyocytes were randomly divided into three groups:high glucose plus high insulin group(model group);high glucose and insulin plus ERK1/2 inhibitor group (treated group);serum free group(control group).Two indexes of cardiomyocyte hypertrophy were examined:cellular surface area and total protein content of cardiomyocytes.The expression of CT-1 mRNA was detected with RT-PCR.Results:1.The cardiac muscle cell surface increased significantly(P＜0.001)in model group as compared with that in control group.In ERK1/2 inhibitor treated group,the cardiac muscle cell surface decreased significantly(P＜0.05)as compared with that in model group and increased significantly(P＜0.01)as compared with that in control group.2.The total protein content of cardiac muscle cells increased significantly (P＜0.001)in model group as compared with that in control group.In ERK1/2 inhibitor treated group,the total protein content decreased significantly(P＜0.05)as compared with that in model group and increased significantly(P＜0.01)as compared with that in control group.3.CT-1 mRNA expression of cardiac muscle cells increased significantly(P＜0.01) in model group as compared with that in control group.In ERK1/2 inhibitor treated group,CT-1 mRNA expression did not changed significantly as compared with that in model group.Conclusion:ERK1/2 inhibitor might have inhibitory effects on cardiomyocyte hypertrophy induced by high glucose and insulin.The mechanisms may be that ERK1/2 inhibitor might involve in the processes of cardiomyocyte hypertrophy induced by high glucose and insulin through affecting the signaling molecules of downstream of CT-1 or independent of CT-1.