Ischemia-stimulated glucose uptake does not require catecholamines in rat heart.
The authors tested the hypothesis that ischemia stimulates glucose uptake in rat heart independent of the insulin signaling pathway and independent of endogenous catecholamines. Isolated working rat hearts were perfused with Krebs-Henseleit buffer containing [2-3H]glucose (5 mmol/l, 0.05 muCi/ml) and Na-oleate (0.4 mmol/l) with or without the phosphatidylinositol 3-kinase inhibitor wortmannin (3 mumol/l). Insulin (1 mU/ml) was added to the perfusate in the middle of the experiments or the hearts were subjected to 30 min of low-flow ischemia (75% reduction in coronary flow) followed by 15 min of reperfusion. In a separate group, hearts were subjected to ischemia and reperfusion in the presence of propranolol (10 mumol/l) plus phentolamine (10 mumol/l). Cardiac power was stable but decreased (-75%) during ischemia. Both insulin and ischemia increased glucose uptake (P < 0.01). Glucose uptake returned to pre-ischemic values during reperfusion. Wortmannin completely inhibited insulin-stimulated glucose uptake and glycogen synthesis, but did not affect the ischemia-stimulated glucose uptake or glycogen resynthesis during reperfusion. Full adrenergic blockade did not abolish the ischemia-stimulated glucose uptake. The authors conclude that: (1) insulin and ischemia increase glucose uptake through different mechanisms; (2) ischemia-stimulated glucose uptake is not catecholamine mediated: and (3) glycogen resynthesis during reperfusion is independent of PI3-K.
Doenst
T
T
Department of Internal Medicine, University of Texas-Houston Medical School 77030, USA.
Taegtmeyer
H
H
D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D003847:Deoxyglucose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism; D006321:Heart / Q000503:physiopathology; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D002395:Catecholamines; D006003:Glycogen; D003847:Deoxyglucose; D005947:Glucose