Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China.
State Key Laboratory of Diabetes and Obesity Surgery, Qilu Hospital of Shandong University, Jinan, China.
J Diabetes Investig. 2019 May;10(3):626-638. doi: 10.1111/jdi.12948. Epub 2018 Nov 2.
AIMS/INTRODUCTION: 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.
目的/引言：十二指肠空肠旁路（DJB）手术已被报道可有效缓解糖尿病心肌病（DCM）。然而，其具体机制仍知之甚少。本研究旨在确定 DJB 后心肌葡萄糖摄取（MGU）的变化及其对 DCM 的影响。
采用高脂肪饮食和低剂量链脲佐菌素诱导糖尿病大鼠，进行 DJB 和假手术，以普通饮食喂养的大鼠作为对照。在指定的时间点测量体重、食物摄入量、葡萄糖稳态和脂质谱。通过经胸超声心动图和血流动力学测量评估心功能。通过一系列形态计量学分析和透射电镜评估心脏重构。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体（GLUT；GLUT1 和 GLUT4）、心肌胰岛素信号和 GLUT-4 易位相关蛋白，以阐明潜在机制。
与假手术组相比，DJB 组表现出收缩和舒张心功能的恢复，以及心脏肥大、心脏纤维化、脂质沉积和超微结构紊乱的显著缓解，而体重减轻则无关。此外，DJB 组表现出心肌胰岛素信号增强，AKT 底物 160 kDa（AS160）和 TBC1D1 的过度磷酸化，以及可溶性 N-乙基马来酰亚胺敏感因子附着蛋白受体蛋白的保留，促进 GLUT-4 向心肌细胞表面易位并恢复 MGU。
本研究结果提供了证据，表明 DJB 后 MGU 的恢复通过促进 GLUT-4 易位缓解 DCM，提示如果正确实施，DJB 可能成为治疗人类 DCM 的一种选择。
