Effect of diabetes and fasting on GLUT-4 (muscle/fat) glucose-transporter expression in insulin-sensitive tissues. Heterogeneous response in heart, red and white muscle.
1. GLUT-4 glucose-transporter protein and mRNA levels were assessed in heart, red muscle and white muscle, as well as in brown and white adipose tissue from 7-day streptozotocin-induced diabetic and 48 h-fasted rats. 2. In agreement with previous data, white adipose tissue showed a substantial decrease in GLUT-4 mRNA and protein levels in response to both diabetes and fasting. Similarly, GLUT-4 mRNA and protein markedly decreased in brown adipose tissue in both insulinopenic conditions. 3. Under control conditions, the level of expression of GLUT-4 protein content differed substantially in heart, red and white skeletal muscle. Thus GLUT-4 protein was maximal in heart, and red muscle had a greater GLUT-4 content compared with white muscle. In spite of the large differences in GLUT-4 protein content, GLUT-4 mRNA levels were equivalent in heart and red skeletal muscle. 4. In heart, GLUT-4 mRNA decreased to a greater extent than GLUT-4 protein in response to diabetes and fasting. In contrast, red muscle showed a greater decrease in GLUT-4 protein than in mRNA in response to diabetes or fasting, and in fact no decrease in GLUT-4 mRNA content was detectable in fasting. On the other hand, preparations of white skeletal muscle showed a substantial increase in GLUT-4 mRNA under both insulinopenic conditions, and that was concomitant to either a modest decrease in GLUT-4 protein in diabetes or to no change in fasting. 5. These results indicate that (a) the effects of diabetes and fasting are almost identical and lead to changes in GLUT-4 expression that are tissue-specific, (b) white adipose tissue, brown adipose tissue and heart respond similarly to insulin deficiency by decreasing GLUT-4 mRNA to a larger extent than GLUT-4 protein, and (c) red and white skeletal muscle respond to insulinopenic conditions in a heterogeneous manner which is characterized by enhanced GLUT-4 mRNA/protein ratios.
Camps
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M
Department de Bioquimica i Fisiologia, Facultat de Biologia, Universitat de Barcelona, Spain.
Castelló
A
A
Muñoz
P
P
Monfar
M
M
Testar
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X
Palacín
M
M
Zorzano
A
A
D000273:Adipose Tissue / Q000378:metabolism / Q000502:physiology; D002001:Adipose Tissue, Brown / Q000378:metabolism / Q000502:physiology; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D005215:Fasting / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D051275:Glucose Transporter Type 4; D007328:Insulin / Q000172:deficiency* / Q000502:physiology; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000235:genetics* / Q000378:metabolism; D009124:Muscle Proteins; D009132:Muscles / Q000378:metabolism / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains
D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; C495694:Slc2a4 protein, rat