Hypoxia and contractions do not utilize the same signaling mechanism in stimulating skeletal muscle glucose transport.
We have investigated whether hypoxia and muscle contractions stimulate glucose transport in perfused rat muscle to the same extent, additively and with the same sensitivity to the microbial products calphostin C and wortmannin. Hindlimb glucose uptake increased gradually from 3.4+/-0.5 to a maximal level of 12.7+/-0.6 micromol g-1 h-1 (n=11) after 50 min of hypoxia. Compared with hypoxia, the effect of maximal electrical stimulation of the sciatic nerve on muscle glucose uptake was more than two-fold higher (27+/-2 micromol g-1 h-1 (n=14)). This was due to a higher contraction- vs. hypoxia-induced glucose transport rate in oxidative fibers. The stimulatory effect of hypoxia and electrical stimulation was not additive. Contraction-induced muscle glucose transport was inhibitable by both calphostin C and wortmannin in the micromolar range, whereas the effect of hypoxia was totally insensitive to these drugs. Our data suggest that diacylglycerol/phorbol ester-sensitive protein kinase C is involved in stimulation of muscle glucose transport by contractions and that in contrast to the prevailing concept, hypoxia and contractions do not stimulate muscle glucose transport by the same signaling mechanism.
Wojtaszewski
J F
JF
Copenhagen Muscle Research Centre, August Krogh Institute, University of Copenhagen, Denmark. jwojtaszew@aki.ku.dk
Laustsen
J L
JL
Derave
W
W
Richter
E A
EA
D000730:Androstadienes / Q000008:administration & dosage; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004558:Electric Stimulation; D005947:Glucose / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology*; D007261:Infusions, Intra-Arterial; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D009281:Naphthalenes / Q000008:administration & dosage / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D000077191:Wortmannin
D000730:Androstadienes; D009281:Naphthalenes; C058819:calphostin C; D005947:Glucose; D000077191:Wortmannin