Effect of exenatide on the cardiac expression of adiponectin receptor 1 and NADPH oxidase subunits and heart function in streptozotocin-induced diabetic rats

Abstract

BackgroundThis study investigated the effect of exenatide on the cardiac expression of adiponectin receptor 1 and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits and heart function in streptozotocin-induced diabetic rats.MethodsMale Sprague–Dawley rats were randomly divided into four groups, i.e. control group, diabetic group, diabetic treated with low doses of exenatide (2 μg · kg−1.d−1) and diabetic treated with high doses of exenatide (10 μg · kg−1.d−1). Diabetes was induced by intraperitoneal injection of streptozotocin (65 mg/kg body weight). At the termination after exenatide treatment for eight weeks, following anesthesia of the rats, a catheter was inserted into the left ventricle through the right common carotid artery for measurement of left ventricular pressure, which included left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and the maximal rate of rise and decline of ventricular pressure (±dp/dt[max]). Plasma and myocardial adiponectin levels, and the expressions of myocardial adiponectin receptor 1, p22phox, NADPH oxidase 4 (NOX4), glucose transporter type 4 (Glut4), AMPK-α, phosphorylated-AMPK-α, connective tissue growth factor (CTGF) and copper zinc superoxide dismutase (Cu-Zn-SOD) were assayed.ResultsHeart function, plasma adiponectin levels, the protein expression of myocardial phosphorylated-AMPK-α, the mRNA expression of myocardial Glut4, and the positive expression of myocardial Cu-Zn-SOD were significantly decreased in diabetic. The protein expression of myocardial adiponectin receptor 1, the mRNA expression of myocardial p22phox and NOX4, and the positive expression of myocardial CTGF were significantly increased in diabetic. Low and high doses of exenatide treatment significantly attenuated these changes in diabetic rats.ConclusionsThese results suggest that exenatide may contribute to the improvement of the heart function in diabetic rats by down-regulating the expression of myocardial adiponectin receptor 1, p22phox and NOX4, and up-regulating plasma adiponectin level and the expression of myocardial AMPK-α, Glut4 and Cu-Zn-SOD.

Adipocyte-Specific Deficiency of NADPH Oxidase 4 Delays the Onset of Insulin Resistance and Attenuates Adipose Tissue Inflammation in Obesity

“…This elevated level of circulating adiponectin could have a beneficial effect on the liver, potentially resulting in the reduced liver inflammation as well as reduced plasma triglycerides and cholesterol we have shown. Consistent with this notion, several other reports showed that increased adiponectin was associated with increased activity of AMPK and reduced NOX4-derived ROS, and showed improvements in heart and podocyte function in obesity and diabetes 30, 31 . In contrast to previous speculation that adiponectin reduces NOX4 activity, leading to improvement of tissue function 30, 31 , our study demonstrates that ablation of NOX4 activity increases plasma adiponectin, leading to improved liver function.…”

“…Consistent with this notion, several other reports showed that increased adiponectin was associated with increased activity of AMPK and reduced NOX4-derived ROS, and showed improvements in heart and podocyte function in obesity and diabetes 30, 31 . In contrast to previous speculation that adiponectin reduces NOX4 activity, leading to improvement of tissue function 30, 31 , our study demonstrates that ablation of NOX4 activity increases plasma adiponectin, leading to improved liver function. We also speculate that the reason why adiponectin levels are elevated after 12 and 16 weeks of HFHS feeding in mice with adipocyte specific-NOX4 ablation is due to the fact that reduced inflammation in adipose tissue leads to increased adiponectin production from adipocytes.…”

NADPH Oxidase 2 Mediates Myocardial Oxygen Wasting in Obesity

“…Even though the systemic effects of reduced NOX2 activity in obesity were subtle in our hands, the cardiac effects were more profound. Diabetes and obesity have been shown to increase myocardial NOX2 activity with both increased expression and recruitment of catalytic subunits to the plasma membrane and elevated ROS production [8,9,13,14,42,43]. Our data support this by showing elevated levels of EOH in cardiac tissue in DIO mice, which is primarily a product of increased superoxide.…”

Combination treatment of adipose-derived stem cells and adiponectin attenuates pulmonary arterial hypertension in rats by inhibiting pulmonary arterial smooth muscle cell proliferation and regulating the AMPK/BMP/Smad pathway

“…We also confirmed that RV function was more effectively improved by ADSCs-APN transplantation rather than ADSC therapy alone. Although the observed beneficial effects of APN are incompletely understood, it is generally believed to exert its effects by decreasing oxidative stress of myocardial cells ( 52 ). Further studies are necessary to elucidate these gene-related mechanisms in myocardial cell lines.…”