Glucose metabolism in perfused mouse hearts overexpressing human GLUT-4 glucose transporter

Glucose and fatty acid metabolism was assessed in isolated working hearts f rom control C57BL/KsJ-m+/+db mice and transgenic mice overexpressing the hu man GLUT-4 glucose transporter (db/+-hGLUT-4). Heart rate, coronary flow, c ardiac output, and cardiac power did not differ between control hearts and hearts overexpressing GLUT-4. Hearts overexpressing GLUT-4 had significantl y higher rates of glucose uptake and glycolysis and higher levels of glycog en after perfusion than control hearts, but rates of glucose and palmitate oxidation were not different. Insulin (1 mU/ml) significantly increased gly cogen levels in both groups. Insulin increased glycolysis in control hearts but not in GLUT-4 hearts, whereas glucose oxidation was increased by insul in in both groups. Therefore, GLUT-4 overexpression increases glycolysis, b ut not glucose oxidation, in the heart. Although control hearts responded t o insulin with increased rates of glycolysis, the enhanced entry of glucose in the GLUT-4 hearts was already sufficient to maximally activate glycolys is under basal conditions such that insulin could not further stimulate the glycolytic rate.