HYPERGLYCEMIA ACTIVATES GLUCOSE-TRANSPORT IN RAT SKELETAL-MUSCLE VIA A CA2+-DEPENDENT MECHANISM

We investigated the acute effect of hyperglycemia on 3-O-methylglucose transport in isolated rat epitrochlearis muscles, High levels of glucose (20 mmol/l) induced an approximately twofold increase in the rate of glucose transport when compared with muscles exposed to a low level of glucose (8 mmol/l) (P < 0.001), The hyperglycemic effect was additive to the effects of both insulin and exercise on the glucose transport rates, Dantrolene (25 mu mol/l), a potent inhibitor of Ca2+ release from the sarcoplasmic reticulum, blocked the ability of hyperglycemia to increase glucose transport by 73% (P < 0.01), Although dantrolene had no effect on the non-insulin-stimulated or the insulin-stimulated glucose transport rates during normoglycemic conditions, the effect of exercise was completely blocked in the presence of dantrolene (P < 0.01), Inhibition of phosphatidylinositol (PI) 3-kinase by wortmannin (500 mmol/l) had no effect on the activation of glucose transport by hyperglycemia, whereas the insulin-stimulated glucose transport was completely abolished (P < 0.001), These findings suggest that hyperglycemia activates glucose transport by a Ca2+ dependent pathway, The signaling system for this Ca2+ dependent activation of glucose transport does not involve the activation of PI 3-kinase and is separate from the mass-action effect of glucose on glucose transport.