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

Abstract

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; GLUT 1 and GLUT 4), 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 kD a ( AS 160) and TBC 1D1, 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.

Gynura divaricata exerts hypoglycemic effects by regulating the PI3K/AKT signaling pathway and fatty acid metabolism signaling pathway

“…PKM1/2 is involved in glycolysis, which is closely related to the occurrence of diabetes 34,35 . GLUT4 is a glucose carrier/transporter located on the cell membrane 36 . A number of literature have reported that the increase of GLUT4 expression promotes the uptake and utilization of glucose by cells, thereby playing an integral role in the treatment of diabetes 37,38 .…”

Obesity, metabolic syndrome and bariatric surgery: A narrative review

“…There are several studies on basic mechanistic research of BS. In diabetic rats, the restoration of myocardial glucose uptake alleviates diabetic cardiomyopathy after duodenal-jejunal bypass surgery through facilitating myocardial glucose transporter (GLUT; GLUT1 and GLUT4) translocation 15 . Although BS can treat morbid obesity, until the mechanism can be clarified, we imagine that the beneficial effects of surgical treatment could also be achieved through non-surgical devices.…”

Exercise as A Potential Therapeutic Target for Diabetic Cardiomyopathy: Insight into the Underlying Mechanisms

“…Under normal physiological conditions, glucose transporter-4 (GLUT-4), an intracellular protein, is translocated to the cell membrane in response to insulin, where it facilitates glucose uptake and utilization [48,49]. However, in diabetes, the expression and function of GLUT-4 are compromised, leading to a marked reduction in glucose transport and impaired energy utilization in the myocardium [50]. However, many studies have reported that moderate exercise can reverse these effects by increasing GLUT-4 expression and glucose transport, thereby activating the pyruvate dehydrogenase complex [51].…”