Restoration of myocardial glucose uptake with facilitated myocardial glucose transporter 4 translocation contributes to alleviation of diabetic cardiomyopathy in rats after duodenal-jejunal bypass.
Restoration of myocardial glucose uptake with facilitated myocardial glucose transporter 4 translocation contributes to alleviation of diabetic cardiomyopathy in rats after duodenal-jejunal bypass.
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促进心肌葡萄糖转运蛋白 4 易位恢复心肌葡萄糖摄取有助于减轻十二指肠空肠旁路术后大鼠糖尿病心肌病
DOI：
10.1111/jdi.12948
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发表时间：
2019-05
影响因子：
3.2
通讯作者：
Liu S
中科院分区：
文献类型：
--
作者：
Huang X;Wu D;Cheng Y;Zhang X;Liu T;Liu Q;Xia P;Zhang G;Hu S;Liu S
据报道，十二指肠空肠旁路（DJB）手术可有效缓解糖尿病心肌病（DCM）。然而，具体机制在很大程度上仍然未知。本研究旨在探讨DJB后心肌葡萄糖摄取（MGU）的变化及其对DCM的影响。在高脂饮食和低剂量链脲佐菌素诱导的糖尿病大鼠中进行十二指肠空肠旁路和假手术，以普通饲料喂养的大鼠作为对照。在指定时间点测量体重、摄食量、葡萄糖稳态和脂质特征。通过经胸超声心动图和血流动力学测定评价心功能。通过一系列形态测量分析和透射电镜沿着评估心脏重构。使用氟-18标记的氟脱氧葡萄糖进行正电子发射断层扫描以评估体内MGU。此外，还研究了心肌葡萄糖转运蛋白（GLUT; GLUT 1和GLUT 4）、心肌胰岛素信号和GLUT-4易位相关蛋白，以阐明其潜在机制。与假手术组相比，DJB组显示收缩和舒张功能恢复，心肌肥厚、心肌纤维化、脂质存款和超微结构紊乱沿着显著缓解，而与体重减轻无关。此外，DJB组显示心肌胰岛素信号传导上调、160 kDa AKT底物（AS 160）和TBC 1D 1的过度磷酸化，以及保留的可溶性N-乙基马来酰亚胺敏感因子附着蛋白受体蛋白，沿着，促进GLUT-4易位至心肌细胞表面并恢复MGU。目前的研究结果提供了证据表明，MGU的恢复通过促进GLUT-4易位与DJB后DCM的缓解有关，这表明如果适当实施，可能是治疗人类DCM的潜在选择。
Duodenal‐jejunal bypass (DJB) surgery has been reported to effectively relieve diabetic cardiomyopathy (DCM). However, the specific mechanisms remain largely unknown. The present study was designed to determine the alterations of myocardial glucose uptake (MGU) after DJB and their effects on DCM. Duodenal‐jejunal bypass and sham surgeries were carried out in diabetic rats induced by a high‐fat diet and a low dose of streptozotocin, with chow‐diet fed rats as controls. Bodyweight, food intake, glucose homeostasis and lipid profiles were measured at indicated time‐points. Cardiac function was evaluated by transthoracic echocardiography and hemodynamic measurement. Cardiac remodeling was assessed by a series of morphometric analyses along with transmission electron microscopy. Positron‐emission tomography with fluorine‐18 labeled fluorodeoxyglucose was carried out to evaluate the MGU in vivo. Furthermore, myocardial glucose transporters (GLUT; GLUT1 and GLUT4), myocardial insulin signaling and GLUT‐4 translocation‐related proteins were investigated to elucidate the underlying mechanisms. The DJB group showed restored systolic and diastolic cardiac function, along with significant remission in cardiac hypertrophy, cardiac fibrosis, lipid deposit and ultrastructural disorder independent of weight loss compared with the sham group. Furthermore, the DJB group showed upregulated myocardial insulin signaling, hyperphosphorylation of AKT substrate of 160 kDa (AS160) and TBC1D1, along with preserved soluble N‐ethylmaleimide‐sensitive factor attachment protein receptor proteins, facilitating the GLUT‐4 translocation to the myocardial cell surface and restoration of MGU. The present findings provide evidence that restoration of MGU is implicated in the alleviation of DCM after DJB through facilitating GLUT‐4 translocation, suggesting a potential choice for treatment of human DCM if properly implemented.
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影响因子：
4.9
作者：
de Simone G;Devereux RB;Chinali M;Lee ET;Galloway JM;Barac A;Panza JA;Howard BV
通讯作者：
Howard BV
影响因子：
8.2
作者：
Bugger, Heiko;Abel, E. Dale
通讯作者：
Abel, E. Dale
DOI：
10.1152/ajpendo.2000.279.5.e1104
发表时间：
2000-11-01
影响因子：
5.1
作者：
Belke, DD;Larsen, TS;Severson, DL
通讯作者：
Severson, DL
影响因子：
29
作者：
Chen S;Wasserman DH;MacKintosh C;Sakamoto K
通讯作者：
Sakamoto K
影响因子：
39.3
作者：
Cook, Stuart A.;Varela-Carver, Anabel;Camici, Paolo G.
通讯作者：
Camici, Paolo G.