Changes Of Expression Of GLUT1and GLUT4mRNA In Diabetic Rat Myocardium With Different Blood Glucose Levels

BACKGROUNDIn our county, the rate of diabetes mellitus (DM) in adults has reached to9.7%, which becomes one of the most important diseases with high health risk. DM is a significant risk factor for coronary disease, and myocardial infarction is an important cause of death, among which DM accounts for19.6%-38%.80%of DM patients died of cardiac events. As a result, blood glucose control is overemphasized in order to decrease cardiac events. However, a lot of evidences based medicine from ACCORD, VADT, ADVANCE showed that it could not decrease cardiac events, but may increase those events. Therefore blood glucose control levels has become the focus issue. How to prevent myocardial infarction and control blood glucose levels, has become an important problem in DM treatment. There may exist compensatory mechanism in diabetic patients, which can protect bodies from hyperglycemic toxicity. When blood glucose level decreases too fast, there may be short of enough glucose in cells and may lead to organ dysfunction, which is according to results based medicine from ACCORD, VADT, ADVANCE. The delivery of glucose from blood to the myocardial cells requires the insulin mediated glucose transporters (GLUTs), which may be the most important factors of the delivery and may be closely related to energy metabolism. GLUTs in human include GLUT1-7. Our study showed that chronic high blood glucose levels could decrease GLUT1and GLUT3, and their levels had negative correlation with blood glucose levels. Thus, there may exist compensatory mechanism in brain with DM in order to adapt to high blood glucose levels. Hyperglycemia pre-accommodation (HGPA) is proposed in diabetic patients. GLUT1and GLUT4are the major glucose transporters in myocardial cells. Whether there also exist HGPA in myocardial and how to control blood glucose levels to improve prognosis, are significant problems to be solved. Our study used DM rat model to discuss expression changes of GLUT1and GLUT4mRNA and the relationship between them and blood glucose levels. And HGPA was initially proved.MATERIALS AND METHODSDiabetic model induced by streptozocin (STZ) was prepared in Wistar rats and their blood glucose levels (BGL) were controlled by insulin. Divide these rats into5groups:normal control group (NC group, in normal blood glucose level) and diabetes mellitus group (DM group, in higher blood glucose level with normal matched comparison). DM group was divided into four groups to more forward a single step in accordance with different blood glucose levels:BGL uncontrolled group (DM1group)、BGL badly controlled group (DM2group)、BGL generally controlled group (DM3group)、BGL well controlled group (DM4group), and the blood glucose levels of diabetic rats were controlled at4levels of>16.7mmol/L (DM1group)、14～16.7mmol/L (DM2group),10～14mmol/L (DM3group) and<10mmol/L (DM4group). The growth conditions of rats were observed during experiment. Put rats to death after12weeks and cardiac muscular tissue was preserved. General indexes (body wight, blood glucose levels and haemoglobinAlc) of animals were examined. The expression of GLUT1and GLUT4mRNA was detected with RT-PCR technique.RESULTSAll diabetic rats presented classic clinical symptoms. Results showed that expression of GLUT1and GLUT4mRNA in diabetic rat myocardium detected with RT-PCR technique decreased. Expression of the two factors was negatively correlated with blood glucose levels. And the downswing was more significant as blood glucose level increased.CONCLUSION1. In high blood glucose environment, levels of GLUT1and GLUT4mRNA expression may decrease in diabetic rat myocardium, and the degree of reduction presents negative correlation with blood glucose concentration.2. The adaptive changes of GLUT1and GLUT4mRNA in cardiac muscular tissue as blood glucose concentration increases may protect heart from the damage induced by hyperglycemia. On the other hand, the changes may be concerned with the development progress of diabetic cardiopathy.SIGNIFICANCEOur study used DM rat model to discuss expression changes of GLUT1, GLUT4mRNA and the relationship between them and blood glucose levels. And HGPA was initially proved. The present and subsequent studies may be helpful for clinical treatment of DM. It may be also worthy to clinical practice and theoretical significance.