Restoration of myocardial glucose uptake with facilitated myocardial glucose transporter 4 translocation contributes to alleviation of diabetic cardiomyopathy in rats after duodenal-jejunal bypass.

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.

MATERIALS AND METHODS

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.

RESULTS

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.

CONCLUSIONS

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.