Glucose metabolism in perfused mouse hearts overexpressing human GLUT-4 glucose transporter.
Glucose and fatty acid metabolism was assessed in isolated working hearts from control C57BL/KsJ-m+/+db mice and transgenic mice overexpressing the human GLUT-4 glucose transporter (db/+-hGLUT-4). Heart rate, coronary flow, cardiac output, and cardiac power did not differ between control hearts and hearts overexpressing GLUT-4. Hearts overexpressing GLUT-4 had significantly higher rates of glucose uptake and glycolysis and higher levels of glycogen after perfusion than control hearts, but rates of glucose and palmitate oxidation were not different. Insulin (1 mU/ml) significantly increased glycogen levels in both groups. Insulin increased glycolysis in control hearts but not in GLUT-4 hearts, whereas glucose oxidation was increased by insulin in both groups. Therefore, GLUT-4 overexpression increases glycolysis, but not glucose oxidation, in the heart. Although control hearts responded to insulin with increased rates of glycolysis, the enhanced entry of glucose in the GLUT-4 hearts was already sufficient to maximally activate glycolysis under basal conditions such that insulin could not further stimulate the glycolytic rate.
Belke
D D
DD
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada T2N 4N1.
Larsen
T S
TS
Gibbs
E M
EM
Severson
D L
DL
D000818:Animals; D003847:Deoxyglucose / Q000378:metabolism; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4; D006003:Glycogen / Q000378:metabolism; D006019:Glycolysis; D006321:Heart / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009004:Monosaccharide Transport Proteins / Q000235:genetics* / Q000502:physiology; D009124:Muscle Proteins; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D019308:Palmitic Acid / Q000378:metabolism; D010477:Perfusion; D014316:Tritium
D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495692:SLC2A4 protein, human; C495693:Slc2a4 protein, mouse; D014316:Tritium; D019308:Palmitic Acid; D006003:Glycogen; D003847:Deoxyglucose; D005947:Glucose