Enhancement of glucose uptake in stunned myocardium: role of glucose transporter.
This study quantifies the myocardial glucose uptake and clarifies the pathway of augmented glucose uptake in myocardium reperfused after a brief period of ischemia (stunned myocardium). The glucose uptake rate was determined from the time course of the sugar phosphate (SP) resonance in rat myocardium (d[SP]/dt) with 31P nuclear magnetic resonance after the substitution of glucose with its analog 2-deoxyglucose. The d[SP]/dt in stunned myocardium [1.03 +/- 0.05 (SE) micromol x g wet wt(-1) x min(-1); n = 8] increased significantly compared with nonischemic control myocardium (0.18 +/- 0.03 micromol x g wet wt(-1) x min(-1); n = 8; P < 0.0001), reaching the maximal stimulatory uptake rate during exposure to insulin (1.05 +/- 0.04 micromol x g wet wt(-1) x min(-1); n = 8). Twenty minutes after reperfusion, the d[SP]/dt was still augmented (0.41 +/- 0.05 micromol x g wet wt(-1) x min(-1); n = 5; P < 0.05 vs. control myocardium). To elucidate further the mechanism of augmented glucose uptake, N6-(L-2-phenylisopropyl)-adenosine (PIA; 100 micromol/l), a potent blocker of the glucose transporter, was administered to stunned hearts and, as a control, to insulin-stimulated hearts. PIA significantly and comparably inhibited the increase in d[SP]/dt in stunned myocardium (0.36 +/- 0.07 micromol x g wet wt(-1) x min(-1); n = 4; P < 0.0001 vs. without PIA) and in insulin-stimulated myocardium (0.38 +/- 0.02 micromol x g wet wt(-1) x min(-1); n = 4; P < 0.0001 vs. without PIA). These results indicate that the augmented glucose uptake in stunned myocardium is maintained by the glucose transporter, the amount of which is almost equal to that which can be maximally recruited by insulin.
Hashimoto
K
K
First Department of Medicine, Osaka University Medical School, Suita, Japan.
Nishimura
T
T
Ishikawa
M
M
Koga
K
K
Mori
T
T
Matsuda
S
S
Hori
M
M
Kusuoka
H
H
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D003847:Deoxyglucose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006321:Heart / Q000502:physiology / Q000503:physiopathology*; D000860:Hypoxia; D066298:In Vitro Techniques; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D017682:Myocardial Stunning / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D010758:Phosphorus; D051381:Rats; D017207:Rats, Sprague-Dawley; D013403:Sugar Phosphates / Q000378:metabolism
D009004:Monosaccharide Transport Proteins; D010710:Phosphates; D013403:Sugar Phosphates; D010725:Phosphocreatine; D010758:Phosphorus; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D005947:Glucose