title: Skeletal muscle signaling associated with impaired glucose tolerance in spinal cord-injured men and the effects of contractile activity.
abstract: The mechanisms underlying poor glucose tolerance in persons with spinal cord injury (SCI), along with its improvement after several weeks of neuromuscular electrical stimulation-induced resistance exercise (NMES-RE) training, remain unclear, but presumably involve the affected skeletal musculature. We, therefore, investigated skeletal muscle signaling pathways associated with glucose transporter 4 (GLUT-4) translocation at rest and shortly after a single bout of NMES-RE in SCI (n = 12) vs. able-bodied (AB, n = 12) men. Subjects completed an oral glucose tolerance test during visit 1 and ≈90 NMES-RE isometric contractions of the quadriceps during visit 2. Muscle biopsies were collected before, and 10 and 60 min after, NMES-RE. We assessed transcript levels of GLUT-4 by quantitative PCR and protein levels of GLUT-4 and phosphorylated- and total AMP-activated protein kinase (AMPK)-α, CaMKII, Akt, and AS160 by immunoblotting. Impaired glucose tolerance in SCI was confirmed by higher (P < 0.05) plasma glucose concentrations than AB at all time points after glucose ingestion, despite equivalent insulin responses to the glucose load. GLUT-4 protein content was lower (P < 0.05) in SCI vs. AB at baseline. Main group effects revealed higher phosphorylation in SCI of AMPK-α, CaMKII, and Akt (P < 0.05), and Akt phosphorylation increased robustly (P < 0.05) following NMES-RE in SCI only. In SCI, low skeletal muscle GLUT-4 protein concentration may, in part, explain poor glucose tolerance, whereas heightened phosphorylation of relevant signaling proteins (AMPK-α, CaMKII) suggests a compensatory effort. Finally, it is encouraging to find (based on Akt) that SCI muscle remains both sensitive and responsive to mechanical loading (NMES-RE) even ≈22 yr after injury.
authors.affiliation: Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama;
authors.forename: Ceren
authors.initials: C
authors.lastname: Yarar-Fisher
authors.forename: C Scott
authors.initials: CS
authors.lastname: Bickel
authors.forename: Samuel T
authors.initials: ST
authors.lastname: Windham
authors.forename: Amie B
authors.initials: AB
authors.lastname: McLain
authors.forename: Marcas M
authors.initials: MM
authors.lastname: Bamman
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D004599:Electric Stimulation Therapy / Q000379:methods; D005947:Glucose / Q000378:metabolism; D018149:Glucose Intolerance / Q000378:metabolism* / Q000503:physiopathology; D005951:Glucose Tolerance Test / Q000379:methods; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006801:Humans; D007328:Insulin; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000502:physiology*; D010766:Phosphorylation / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D052097:Quadriceps Muscle / Q000378:metabolism* / Q000502:physiology*; D055070:Resistance Training / Q000379:methods; D012146:Rest / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013116:Spinal Cord / Q000378:metabolism / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000503:physiopathology*; D019415:Torque; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D007328:Insulin; D051057:Proto-Oncogene Proteins c-akt; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D055372:AMP-Activated Protein Kinases; D005947:Glucose
keywords: glucose uptake signaling; neuromuscular electrical stimulation; resistance exercise; skeletal muscle; spinal cord injury