[Change of glucose transporter 4 and its influence on glucose and fatty-acid metabolism in type 2 diabetic myocardium].
OBJECTIVE
To investigate the relationship between sarcolemmal content of glucose transporter 4 (GLUT4) and the myocardial glucose and fatty acid utilization in type 2 diabetes.


METHODS
Twenty-four Sprague-Dawley rats were randomized into four groups: control, HFD/STZ, control/RSG and HFD/STZ/RSG. Sprague-Dawley rats were fed with high-fat diet (40% of the calories was supplied by fat) for 4 weeks, intraperitoneally injected with 35 mg/kg streptozotocin to establish type 2 diabetes model, and 24 diabetic rats were randomized into four groups: HFD/STZ/RSG group [fed with high fat food and given rosiglitazone (3 mg.kg(-1).d(-1)) for 2 weeks], HFD/STZ group (fed with high fat food and given normal saline), control/RSG [fed with normal food and given rosiglitazone (3 mg.kg(-1).d(-1)) for 2 weeks], and control group (fed with normal food and given normal saline). Then the rats were killed and their hearts were taken out to be mounted onto a Langendorff perfusion apparatus to be perfused with Krebs-Henseleit buffer in the presence of 5 mmol/L glucose and 0.4 mmol/L (3)H labeling palmitate. Glucose uptake and (3)H2O collection were used to evaluate the rate of carbohydrate and fatty acid oxidation. The sarcolemmal content of GLUT4 protein was detected by Western blotting method.


RESULTS
Compared with the control group, the diabetic rats had a significantly depression of glucose uptake of the heart [(55 +/- 6) micromol/g dry weight vs (69 +/- 6) micromol/g dry weight, P < 0.01], the oxidation rate of glucose decreased from 25% to 18% and the oxidation rate of palmitate increased from 75% to 82%, and the sarcolemmal GLUT4 content was decreased by 53% after 30 minutes' perfusion. In the HFD/STZ/RSG group the glucose uptake level was (64 +/- 6) micromol/g dry weight, significantly higher than that of the HFD/STZ group (P < 0.05), the proportions of glucose oxidation and fatty acid oxidation were 24% and 76% respectively, and the GLUT4 expression was 92% that of the normal rats, significantly higher than that of the HFD/STZ group (47%, P < 0.01).


CONCLUSIONS
The sarcolemmal GLUT4 content in the type 2 diabetic myocardium is obviously decreased, which may be associated with the decrease of glucose uptake and increase of fatty acid oxygen. Rosiglitazone treatment may exert beneficial effects on the energy substrate utilization by increasing the expression of GLUT4.
Wen
Zhong-yuan
ZY
Department of Endocrinology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Wu
Yong
Y
Li
Yan
Y
Chen
Xiao-lin
XL
Wang
Teng
T
Ouyang
Jing-ping
JP
Li
Geng-shan
GS
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014325:Tromethamine
D005227:Fatty Acids; D051275:Glucose Transporter Type 4; C074097:Krebs-Henseleit solution; D014325:Tromethamine; D005947:Glucose