Abstract: Objective: To determine whether the ERK1/2 inhibitor has an inhibitory effect on cardiomyocyte hypertrophy induced by high glucose and insulin in neonatal rats. Methods: Cardiomyocytes of neonatal Wistar rats were cultured in DMEM containing 10% calf bovine serum for 72 hours, then were treated with high glucose plus high insulin or high glucose and insulin plus ERK1/2 inhibitor in serum free DMEM for another 48 hours. Cells serving as the controls were cultured in DMEM containing 10% calf bovine serum for 72 hours and then were continuously cultured in serum free DMEM for another 48 hours. Two indexes of cardiomyocyte hypertrophy were determined: the cellular surface area and the total protein content of cardiomyocytes. Expression of cardiotrophin-1 (CT-1) mRNA was also determined. Results: The cellular surface area, total protein content, and CT-1 mRNA were significantly increased after treatment with high glucose and insulin compared with the controls. The ERK1/2 inhibitor partially inhibited the increased cellular surface area and the total protein content induced by high glucose and insulin, however, CT-1 mRNA expression was not affected by the ERK1/2 inhibitor in this condition. Conclusion: The ESK1/2 inhibitor might have an inhibitory effect on cardio-myocyte hypertrophy induced by high glucose and insulin, which might be because the ERK1/2 inhibitor affects the signaling molecules at the downstream of CT-1 or is independent of CT-1.

Key words: ERK1/2, Glucose, Insulin, Cardiomyocyte hypertrophy, Rats