Exercise-induced overexpression of key regulatory proteins involved in glucose uptake and metabolism in tetraplegic persons: molecular mechanism for improved glucose homeostasis

Complete spinal cord lesion leads to profound metabolic abnormalities and s triking changes in muscle morphology. Here we assess the effects of electri cally stimulated leg cyclic; (ESLC) on whole body insulin sensitivity, skel etal muscle glucose metabolism, and muscle fiber morphology in five tetrapl egic subjects with complete C-5-C-7 lesions. Physical training (seven ESLC sessions/wk for 8 wk) increased whole body insulin-stimulated glucose uptak e by 33+/-13%, concomitant with a 2.1-fold increase in insulin-stimulated ( 100 mu U/ml) 3-O-methylglucose transport in isolated vastus lateralis muscl e. Physical training led to a marked increase in protein expression of GLUT 4 (378+/-85%), glycogen synthase (526+/-146%), and hexokinase II (204+/-47% ) in vastus lateralis muscle, whereas phosphofructokinase expression (282+/ -97%) was not significantly changed. Hexokinase II activity was significant ly increased, whereas activity of phosphofructokinase, glycogen synthase, a nd citrate synthase was not changed after training. Muscle fiber type distr ibution and fiber area were markedly altered compared to able-bodied subjec ts before ESLC training, with no change noted in either parameter after ECS L training. In conclusion, muscle contraction improves insulin action on wh ole body and cellular glucose uptake in cervical cord-injured persons throu gh a major increase in protein expression of key genes involved in the regu lation of glucose metabolism. Furthermore, improvements in insulin action o n glucose metabolism are independent of changes in muscle fiber type distri bution.