Hyperglycemia activates glucose transport in rat skeletal muscle via a Ca(2+)-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 mumol/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 nmol/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 Ca(2+)-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.
Nolte
L A
LA
Department of Clinical Physiology, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden.
Rincón
J
J
Wahlström
E O
EO
Craig
B W
BW
Zierath
J R
JR
Wallberg-Henriksson
H
H
D019325:3-O-Methylglucose; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D003620:Dantrolene / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D006943:Hyperglycemia / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D008757:Methylglucosides / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors; D005082:Physical Exertion; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D000077191:Wortmannin
D000730:Androstadienes; D004791:Enzyme Inhibitors; D007328:Insulin; D008757:Methylglucosides; D019325:3-O-Methylglucose; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D003620:Dantrolene; D005947:Glucose; D002118:Calcium; D000077191:Wortmannin