The action of cardiotonic steroids on sugar transport in muscle, in vitro

Abstract

1. (1) The membrane transport of sugar in the “intact” rat hemidiaphragm in vitro was studied by measuring the distribution of 3-O- methyl- d-[ 14C]glucose into the intracellular water. Transport was significantly increased in the presence of ouabain and several other cardiac glycosides and aglycones at concentrations (about 10 −5 M) known to inhibit Na + transport. 2. (2) This effect required preincubation of the tissue with the drug and 10 mM glucose and was enhanced by submaximal concentrations of insulin (0.5 munit/ml) in the incubation or preincubation medium. It would seem that a transport and/or binding step is a prerequisite for the action of these drug. 3. (3) Stimulation of transport by ouabain was inhibited by phlorizin or N-ethylmaleimide and was absent when transport was fully activated by supramaximal concentrations of insulin, indicating that cardiotonic steroids affect the stereospecific, insulin-sensitive sugar transport process. 4. (4) Stimulation of transport was prevented by anoxia or uncoupling of oxidative phosphorylation, showing that the process affected by the drug depends on respiratory ATP. 5. (5) Incubation of a K +-free medium produced a stimulatory effect identical in every manner with that of ouabain. This suggests that the effect of cardiotonic steroids on sugar transport is due to their inhibition of a sodium pump. 6. (6) It is suggested there exists in muscle a negative feedback from an aerobic sodium pump to sugar transport and that this is part of the regulatory mechanism whereby the Pasteur effect is exerted at the level of membrane transport.