Polymyxin B inhibits stimulation of glucose transport in muscle by hypoxia or contractions

Glucose transport can be stimulated via two separate pathways in muscle. One is activated by insulin, the other by contractile activity and hypoxia. Polymyxin B, a cationic antibiotic that displaces Ca2+ from anionic phospholipids, is reported to selectively inhibit the stimulation of glucose transport by insulin in muscle. A purpose of the present study was to determine whether the inhibition by polymyxin B is actually restricted to insulin. We found that polymyxin B (250 micrograms/ml) significantly inhibited the stimulation of glucose transport in rat skeletal muscles not only by insulin and vanadate but also by hypoxia, electrical stimulation, and K+. Polymyxin B also decreased the tension developed in response to electrical stimulation or K+. Although polymyxin B inhibited the increase in sugar transport activity induced by insulin and hypoxia, it had no inhibitory effect on sugar transport after it had been stimulated by these agents. These results show that the inhibitory effect of polymyxin B on the stimulation of glucose transport is not specific for insulin action. They suggest that polymyxin B inhibits a step that is common to the two pathways for stimulating glucose transport in skeletal muscle.