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, additive ly 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 mu mol 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 w as more than two-fold higher (27 +/- 2 mu mol g(-1) h(-1) (n=14)). Thi s was due to a higher contraction vs. hypoxia-induced glucose transpor t rate in oxidative fibers. The stimulatory effect of hypoxia and elec trical stimulation was not additive. Contraction-induced muscle glucos e transport was inhibitable by both calphostin C and wortmannin in the micromolar range, whereas the effect of hypoxia was totally insensiti ve to these drugs. Our data suggest that diacylglycerol/phorbol ester- sensitive protein kinase C is involved in stimulation of muscle glucos e transport by contractions and that in contrast to the prevailing con cept, hypoxia and contractions do not stimulate muscle glucose transpo rt by the same signaling mechanism. (C) 1998 Elsevier Science B.V.