Protective effects and mechanism of exenatide on H9C2 cardiomyocytes cultured with high glucose

Abstract

Objective To explore the effect and underlying mechanism of exenatide on the cardiomyocytes through evaluating its impact on adiponectin and its receptors(AdipoR), oxidative stress and endoplasmic reticulum stress in cardiomyocytes cultured with high glucose. Methods H9C2 cardiomyocytes were randomly divided into following four groups (n=3): group A: cardiomyocytes were cultured in normal glucose concentration (5.6 mmol/L); group B: cardiomyocytes were cultured in high glucose concentration (25.5 mmol/L); group C: cardiomyocytes were cultured in high glucose concentration and 10 nmol/L GLP-1; group D: cardiomyocytes were cultured in high glucose concentration and 100 nmol/L GLP-1. Four groups were continued to be cultured for 24 h. The expression of adiponectin, AdipoR1, nicotinamide adenine dinucleotide (NADPH) oxidase subunit (p22phox) nuclear factor E2-related factor2 (Nrf2), and C/EBP homologous protein(CHOP) were analyzed. Differences among groups were compared by one-way analysis of variance, pairwise comparison were conducted using LSD-t test. Results (1)The level of adiponectin, the protein expression of AdipoR1, and the mRNA expression of Nrf2 were significantly decreased in group B than those in group A (760±145 vs 1 490±168; 0.59±0.08 vs 0.91±0.07; 0.56±0.02 vs 1.00 ± 0.00, t= 7.942, 6.922, 10.689; all P<0.05). The protein expression of p22phox, and the mRNA expression of CHOP were significantly increased in group B than those in group A(0.87±0.02 vs 0.56±0.09; 1.58 ± 0.16 vs 1.00 ± 0.00; t=7.591, 5.994; all P<0.05). (2)The levels of adiponectin, AdipoR1 protein expression and the Nrf2 mRNA expression of group C(1 070±142, 0.69±0.02, 0.71±0.09) were significantly higher than those of group B(t=3.372, 2.263, 3.633; all P<0.05). The p22phox protein (0.66 ± 0.04）and CHOP mRNA (1.26 ± 0.28）of group C were markedly lower than those of group B(t=4.716, 3.272，all P< 0.05). (3)The level of adiponectin(1 306 ± 178), the protein expression of AdipoR1(0.82 ± 0.09), and the mRNA expression of Nrf2 (0.91±0.11) were increased in group D than that in group C(t=2.575, 2.349, 4.792; all P<0.05). The mRNA expression of CHOP was decreased in group D than that in group C(t=3.185, P< 0.05). Conclusions Exenatide plays protective role on cardiomyocytes cultured with high glucose. It may abate cardiomyocyte damage induced by oxidative stress and endoplasmic reticulum stress through regulating adiponectin and its signaling pathways. Key words: Glucagon-like peptide 1; Adiponectin; Myocytes, cardiac; Oxidative stress; Endoplasmic reticulum stress; High glucose