EFFECTS OF CA2-STIMULATED AND BASAL GLUCOSE-TRANSPORT IN MUSCLE( IONOPHORE IONOMYCIN ON INSULIN)

There is evidence that an increase in sarcoplasmic Ca2+ stimulates glu cose transport in muscle. Recent studies have provided the apparently conflicting finding that a sustained increase in cytosolic Ca2+ has li ttle effect on basal glucose transport but inhibits insulin-stimulated transport. This study was done to try to explain this discrepancy. Co ntinuous exposure of rat epitrochlearis and soleus muscles to the Ca2 ionophore ionomycin (2 mu M) had no effect on basal 2-deoxyglucose (2 -DG) transport but blunted, by similar to 40%, stimulation of 2-DG tra nsport by insulin. Decreasing Ca2+ in the medium to a very low level p revented this inhibition. Ionomycin induced a small increase in adenos ine 3',5'-cyclic monophosphate (cAMP); however, studies with the prote in kinase A (PKA) inhibitor HA-1004 provided evidence that activation of PKA by cAMP does not mediate the inhibition of glucose transport. W hen muscles were allowed to recover in the absence of ionomycin for 15 min, basal 2-DG transport was significantly increased. Our results ag ree 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 inh ibited. A recovery period that allows this inhibition to wear off unma sks the stimulation of glucose transport by an increase in sarcoplasmi c Ca2+.