Effects of Ca2+ ionophore ionomycin on insulin-stimulated and basal glucose transport in muscle.
There is evidence that an increase in sarcoplasmic Ca2+ stimulates glucose transport in muscle. Recent studies have provided the apparently conflicting finding that a sustained increase in cytosolic Ca2+ has little effect on basal glucose transport but inhibits insulin-stimulated transport. This study was done to try to explain this discrepancy. Continuous exposure of rat epitrochlearis and soleus muscles to the Ca2+ ionophore ionomycin (2 microM) had no effect on basal 2-deoxyglucose (2-DG) transport but blunted, by approximately 40%, stimulation of 2-DG transport by insulin. Decreasing Ca2+ in the medium to a very low level prevented this inhibition. Ionomycin induced a small increase in adenosine 3',5'-cyclic monophosphate (cAMP); however, studies with the protein kinase A (PKA) inhibitor HA-1004 provided evidence that activation of PKA by cAMP does not mediate the inhibition of glucose transport. When muscles were allowed to recover in the absence of ionomycin for 15 min, basal 2-DG transport was significantly increased. Our results agree with previous studies showing that a sustained influx of Ca2+ into the cytoplasm can inhibit insulin-stimulated glucose transport. They further show that stimulation of glucose transport by Ca2+ is also inhibited. A recovery period that allows this inhibition to wear off unmasks the stimulation of glucose transport by an increase in sarcoplasmic Ca2+.
Lee
A D
AD
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Gulve
E A
EA
Chen
M
M
Schluter
J
J
Holloszy
J O
JO
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology; D005947:Glucose / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D015759:Ionomycin / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009132:Muscles / Q000378:metabolism*; D010762:Phosphorylase a / Q000378:metabolism; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides
D007328:Insulin; D007546:Isoquinolines; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D015759:Ionomycin; D006003:Glycogen; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; D000242:Cyclic AMP; D010762:Phosphorylase a; D005947:Glucose; D004837:Epinephrine