title: Exercise-induced overexpression of key regulatory proteins involved in glucose uptake and metabolism in tetraplegic persons: molecular mechanism for improved glucose homeostasis.
abstract: Complete spinal cord lesion leads to profound metabolic abnormalities and striking changes in muscle morphology. Here we assess the effects of electrically stimulated leg cycling (ESLC) on whole body insulin sensitivity, skeletal muscle glucose metabolism, and muscle fiber morphology in five tetraplegic subjects with complete C5-C7 lesions. Physical training (seven ESLC sessions/wk for 8 wk) increased whole body insulin-stimulated glucose uptake by 33+/-13%, concomitant with a 2.1-fold increase in insulin-stimulated (100 microU/ml) 3-O-methylglucose transport in isolated vastus lateralis muscle. Physical training led to a marked increase in protein expression of GLUT4 (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 significantly increased, whereas activity of phosphofructokinase, glycogen synthase, and citrate synthase was not changed after training. Muscle fiber type distribution and fiber area were markedly altered compared to able-bodied subjects before ESLC training, with no change noted in either parameter after ECSL training. In conclusion, muscle contraction improves insulin action on whole body and cellular glucose uptake in cervical cord-injured persons through a major increase in protein expression of key genes involved in the regulation of glucose metabolism. Furthermore, improvements in insulin action on glucose metabolism are independent of changes in muscle fiber type distribution.
authors.affiliation: Sunnaas Hospital, 1450 Nesoddtangen, Norway.
authors.forename: N
authors.initials: N
authors.lastname: Hjeltnes
authors.forename: D
authors.initials: D
authors.lastname: Galuska
authors.forename: M
authors.initials: M
authors.lastname: Björnholm
authors.forename: A K
authors.initials: AK
authors.lastname: Aksnes
authors.forename: A
authors.initials: A
authors.lastname: Lannem
authors.forename: J R
authors.initials: JR
authors.lastname: Zierath
authors.forename: H
authors.initials: H
authors.lastname: Wallberg-Henriksson
mesh_terms: D019325:3-O-Methylglucose / Q000378:metabolism; D001692:Biological Transport; D004599:Electric Stimulation Therapy; D015444:Exercise; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D051275:Glucose Transporter Type 4; D006003:Glycogen / Q000032:analysis; D006006:Glycogen Synthase / Q000096:biosynthesis; D006593:Hexokinase / Q000096:biosynthesis; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007866:Leg; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis; D018485:Muscle Fibers, Skeletal / Q000648:ultrastructure; D009124:Muscle Proteins; D011782:Quadriplegia / Q000378:metabolism* / Q000628:therapy; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000628:therapy
chemical_list: D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495692:SLC2A4 protein, human; D019325:3-O-Methylglucose; D006003:Glycogen; D006006:Glycogen Synthase; D006593:Hexokinase; D005947:Glucose