Stimulation of glucose transport in skeletal muscle by the sodium ionophore monensin.
The tissue/medium distribution of the nonmetabolized glucose analog 3-O-methyl-D-glucose was measured in mouse diaphragm muscle and related to changes in 45Ca influx, Na+ content and Na+-pump activity. In the presence of external Ca2+ the sodium ionophore monensin greatly increased cellular Na+ content (and decreased K+ content) although 86Rb uptake, reflecting Na+-pump activity was increased. Concomitantly, 45Ca influx was stimulated, presumably through activation of Na+-Ca2+ exchange. In parallel to the rise in Ca2+ influx sugar transport was also increased. Sugar transport was also increased by monensin in the nominal absence of external Ca2+, when Ca2+ influx was minimal. To test if monensin releases Ca2+ from intracellular storage sites in the absence of external Ca2+, the ionophore was added to medium perfusing rat hind limb preparations and the total Ca content of muscle mitochondria was determined. When Ca2+ was present in the perfusate, monensin increased the mitochondrial Ca content. In the absence of Ca2+, the mitochondrial Ca content was lower and was further depressed by monensin, suggesting that elevation of internal Na+ by monensin may increase mitochondrial Ca2+ loss via activation of Na+-Ca2+ exchange across the mitochondrial membrane. The above results are consistent with the effect of monensin on sugar transport being due to alterations in Ca2+ distribution. They support the earlier conclusion that regulation of sugar transport in muscle is Ca2+ dependent.
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D005663:Furans / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D006614:Hindlimb; D007700:Kinetics; D008297:Male; D051379:Mice; D008931:Mitochondria, Muscle / Q000378:metabolism; D008985:Monensin / Q000494:pharmacology*; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism
D005663:Furans; D009004:Monosaccharide Transport Proteins; D008985:Monensin; D012964:Sodium; D005947:Glucose; D002118:Calcium