Uniaxial cyclic stretch increases glucose uptake into C2C12 myotubes through a signaling pathway independent of insulin-like growth factor I.
Insulin-like growth factor I (IGF-I), an autocrine/paracrine growth factor involved in myogenesis, has rapid effects on muscle metabolism. In a manner analogous to insulin and mechanical stimuli such as stretch, IGF-I stimulates glucose transport through recruitment of glucose transporters to surface membranes in skeletal muscles. It is known that IGF-I is secreted from skeletal muscle cells in response to stretch. Therefore, we examined whether IGF-I is involved in the mechanism by which mechanical stretch regulates glucose transport using cultured C2C12 myotubes. IGF-I increased 2-deoxy- D-glucose (2-DG) uptake, and this created an additive effect with mechanical stretch, suggesting that these stimuli enhance glucose transport through different mechanisms. In fact, IGF-I-stimulated 2-DG uptake was not blocked by dantrolene (an inhibitor of Ca (2+)release from sarcoplasmic reticulum), whereas the stretch-stimulated effect was abolished. Conversely, the IGF-I-stimulated 2-DG uptake was prevented by phosphatidylinositol 3-kinase inhibitor wortmannin, which did not prevent the stretch-stimulated 2-DG uptake. In addition, experiments using media conditioned by stretched myotubes indicated that a mechanically induced release of locally acting autocrine/paracrine growth factors was not sufficient for induction of 2-DG uptake. Thus, our results demonstrate that mechanical stretch signaling for glucose transport is independent of the mechanism through which IGF-I increases this transport.
Program in Physical and Occupational Therapy, Nagoya University Graduate School of Medicine, Higashi-ku, Nagoya, Japan.
M
M
Iwata
S
S
Suzuki
K
K
Hayakawa
T
T
Inoue
K
K
Naruse
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D003620:Dantrolene / Q000494:pharmacology; D003847:Deoxyglucose / Q000493:pharmacokinetics*; D007328:Insulin / Q000494:pharmacology; D007329:Insulin Antagonists / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology* / Q000502:physiology; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D009125:Muscle Relaxants, Central / Q000494:pharmacology; D052580:Muscle Stretching Exercises; D010507:Periodicity; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013314:Stress, Mechanical; D000077191:Wortmannin
D000730:Androstadienes; D007328:Insulin; D007329:Insulin Antagonists; D009125:Muscle Relaxants, Central; D007334:Insulin-Like Growth Factor I; D003847:Deoxyglucose; D003620:Dantrolene; D000077191:Wortmannin