Regulating effect of exenatide on disorder of calcium signal in neonatal rat cardiomyocytes induced by high glucose

CHEN Zelong; YU Huaixin; CHEN Shujuan; LIU Junying; LIU Wenjuan; DENG Jianxin; WANG Xinyu; YAN Dewen

doi:10.3969/j.issn.1002-266X.2017.06.006

Abstract：Objective To investigate the regulating effect of GLP-1 analogue exenatide (exenatide-4, EX-4) on the disorder of calcium signal in neonatal rat cardiomyocytes induced by high glucose and the cardioprotective mechanism . Methods The neonatal rat cardiomyocytes were isolated and cultured for 24 h, and then were randomly divided into 3 groups:the control group , high glucose group and high glucose +EX-4 group which were separately treated with 25 mmol/L mannitol, 25 mmol/L high glucose and 25 mmol/L high glucose+10 mmol/L EX-4.The frequency of spontaneous Ca 2+spark in cadiomyocyte , field-stimulated calcium transient amplitude and calcium storage capacity were detected by laser scanning confocal microscopy .L-type calcium channel current was recorded by using patch-clamp technique .Results The frequencies of spontaneous Ca 2+spark in cadiomyocytes of the control group , high glucose group and high glucose +EX-4 group were (1.35 ±0.07), (3.86 ±0.27) and (1.99 ±0.15)/(μm· s), respectively.Field-stimulated calcium transi-ent amplitude was 3.95 ±0.08, 3.34 ±0.07 and 4.09 ±0.12.The calcium storage capacities were 4.95 ±0.18, 3.26 ± 0.09 and 4.59 ±0.15, respectively.L-type calcium channel current density at 10 mV were -12.46 ±0.58, -11.28 ± 0.55, and -13.09 ±0.64.In the high glucose group, the frequency of Ca2+spark and the Ca2+transient amplitude were higher than those of the control group (P<0.05 or P<0.01), and calcium storage capacity and L type calcium current density were lower than those in the control group (P<0.05 or P<0.01).In the high glucose+EX-4 group, the frequen-cy of Ca2+spark and the amplitude of Ca 2+transient were higher than those of the high glucose group ( P<0.05 or P<0.01), and calcium storage capacity and L type calcium current density were higher than those of the high glucose group (P<0.05 or P<0.01), while there was no statistically significant difference as compared with those of the control group . Conclusions EX-4 can increase L-type Ca2+current in cardiomyocytes , and reduce the Ca 2+leakage current in the plas-ma, thus effectively correcting the disorder of Ca 2+regulation in cardiomyocytes induced by high glucose .Therefore, EX-4 has good myocardial protective effect on patients with diabetes mellitus .