Thyroid hormone increases basal and insulin-stimulated glucose transport in skeletal muscle. The role of GLUT4 glucose transporter expression.
In skeletal muscle, the main site of insulin-mediated glucose disposal, the major muscle glucose transporter GLUT4 is induced by thyroid hormone. To test the hypothesis that thyroid hormone alters muscle glucose transport, we examined the effect of L-triiodothyronine (T3) on glucose transport and GLUT4 protein content in isolated rat skeletal muscles. Euthyroid rats were treated with or without T3 for 3 days, and [3H]2-deoxy-D-glucose (2-DG) uptake in soleus and extensor digitorum longus (EDL) muscles was measured under conditions in which transport was rate limiting for uptake in the absence or presence of 10 nmol/l insulin. In control animals, insulin stimulated 2-DG uptake sevenfold in soleus and fivefold in EDL. T3 treatment increased basal 2-DG uptake in soleus and EDL by 115 +/- 29% and 136 +/- 23%, respectively, and increased insulin-stimulated 2-DG uptake in soleus and EDL by 55 +/- 9 and 42 +/- 12%, respectively. Immunoblot analysis revealed that T3 treatment increased GLUT4 protein content in soleus by 43 +/- 6% and in EDL by 56 +/- 13%. These data demonstrate that thyroid hormone increases basal and insulin-stimulated glucose transport in skeletal muscle. The percentage increase in insulin-stimulated transport in T3-treated muscles is similar to the increase in GLUT4 protein content, whereas the percentage change in basal transport greatly exceeds the change in GLUT4. Thus, increased insulin-stimulated glucose transport in T3-treated muscle can be accounted for by the induction of GLUT4 protein.(ABSTRACT TRUNCATED AT 250 WORDS)
Weinstein
S P
SP
Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029.
O'Boyle
E
E
Haber
R S
RS
D000818:Animals; D001345:Autoradiography; D001692:Biological Transport / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003847:Deoxyglucose / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4; D007328:Insulin / Q000494:pharmacology; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis* / Q000302:isolation & purification; D009124:Muscle Proteins; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014284:Triiodothyronine / Q000494:pharmacology*; D014316:Tritium
D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495694:Slc2a4 protein, rat; D014284:Triiodothyronine; D014316:Tritium; D003847:Deoxyglucose; D005947:Glucose