Contractile activity restores insulin responsiveness in skeletal muscle of obese Zucker rats.
Both insulin and contraction stimulate glucose transport in skeletal muscle. Insulin-stimulated glucose transport is decreased in obese humans and rats. The aims of this study were (1) to determine if contraction-stimulated glucose transport was also compromised in skeletal muscle of genetically obese insulin-resistant Zucker rats, and (2) to determine whether the additive effects of insulin and contraction previously observed in muscle from lean subjects were evident in muscle from the obese animals. To measure glucose transport, hindlimbs from lean and obese Zucker rats were perfused under basal, insulin-stimulated (0.1 microM), contraction-stimulated (electrical stimulation of the sciatic nerve) and combined insulin-(+)contraction-stimulated conditions. One hindlimb was stimulated to contract while the contralateral leg served as an unstimulated control. 2-Deoxyglucose transport rates were measured in the white gastrocnemius, red gastrocnemius and extensor digitorum longus muscles. As expected, the insulin-stimulated glucose transport rate in each of the three muscles was significantly slower (P < 0.05) in obese rats when compared with lean animals. When expressed as fold stimulation over basal, there was no significant difference in contraction-induced muscle glucose transport rates between lean and obese animals. Insulin-(+)contraction-stimulation was additive in skeletal muscle of lean animals, but synergistic in skeletal muscle of obese animals. Prior contraction increased insulin responsiveness of glucose transport 2-5-fold in the obese rats, but had no effect on insulin responsiveness in the lean controls. This contraction-induced improvement in insulin responsiveness could be of clinical importance to obese subjects as a way to improve insulin-stimulated glucose uptake in resistant skeletal muscle.
Dolan
P L
PL
Department of Biochemistry, School of Medicine, East Carolina University, Greenville, NC 27858.
Tapscott
E B
EB
Dorton
P J
PJ
Dohm
G L
GL
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004558:Electric Stimulation; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction; D009132:Muscles / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D009765:Obesity / Q000235:genetics / Q000503:physiopathology*; D051381:Rats; D011924:Rats, Zucker; D012584:Sciatic Nerve / Q000503:physiopathology
D007328:Insulin; D005947:Glucose