Interactions of exercise training and lipoic acid on skeletal muscle glucose transport in obese Zucker rats.
Exercise training (ET) or the antioxidant R(+)-alpha-lipoic acid (R-ALA) individually increases insulin action in the insulin-resistant obese Zucker rat. The purpose of the present study was to determine the interactions of ET and R-ALA on insulin action and oxidative stress in skeletal muscle of the obese Zucker rat. Animals either remained sedentary, received R-ALA (30 mg x kg body wt(-1) x day(-1)), performed ET (treadmill running), or underwent both R-ALA treatment and ET for 6 wk. During an oral glucose tolerance test, ET alone or in combination with R-ALA resulted in a significant lowering of the glucose (26-32%) and insulin (29-30%) responses compared with sedentary controls. R-ALA alone decreased (19%) the glucose-insulin index (indicative of increased insulin sensitivity), and this parameter was reduced (48-52%) to the greatest extent in the ET and combined treatment groups. ET or R-ALA individually increased insulin-mediated glucose transport activity in isolated epitrochlearis (44-48%) and soleus (37-57%) muscles. The greatest increases in insulin action in these muscles (80 and 99%, respectively) were observed in the combined treatment group. Whereas the improvement in insulin-mediated glucose transport in soleus due to R-ALA was associated with decreased protein carbonyl levels (an index of oxidative stress), improvement because of ET was associated with decreased protein carbonyls as well as enhanced GLUT-4 protein. However, there was no interactive effect of ET and R-ALA on GLUT-4 protein or protein carbonyl levels. These results indicate that ET and R-ALA interact in an additive fashion to improve insulin action in insulin-resistant skeletal muscle. Because the further improvement in muscle glucose transport in the combined group was not associated with additional upregulation of GLUT-4 protein or a further reduction in oxidative stress, the mechanism for this interaction must be due to additional, as yet unidentified, factors.
Saengsirisuwan
V
V
Muscle Metabolism Laboratory, Department of Physiology, University of Arizona College of Medicine, Tucson, Arizona 85721-0093, USA.
Kinnick
T R
TR
Schmit
M B
MB
Henriksen
E J
EJ
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D004798:Enzymes / Q000378:metabolism; D005260:Female; D005951:Glucose Tolerance Test; D051275:Glucose Transporter Type 4; D006321:Heart / Q000033:anatomy & histology; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009765:Obesity / Q000503:physiopathology*; D009929:Organ Size / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010805:Physical Conditioning, Animal; D051381:Rats; D011924:Rats, Zucker; D013237:Stereoisomerism; D008063:Thioctic Acid / Q000494:pharmacology*
D000975:Antioxidants; D004798:Enzymes; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495694:Slc2a4 protein, rat; D008063:Thioctic Acid