| First Author | Luptak I | Year | 2007 |
| Journal | Circulation | Volume | 116 |
| Issue | 8 | Pages | 901-9 |
| PubMed ID | 17679614 | Mgi Jnum | J:139851 |
| Mgi Id | MGI:3810239 | Doi | 10.1161/CIRCULATIONAHA.107.691253 |
| Citation | Luptak I, et al. (2007) Long-term effects of increased glucose entry on mouse hearts during normal aging and ischemic stress. Circulation 116(8):901-9 |
| abstractText | BACKGROUND: A shift of substrate preference toward glucose in the heart is considered a reversion to fetal metabolic profile, but its role in the pathogenesis of cardiac diseases is incompletely understood. METHODS AND RESULTS: We performed a 2-year follow-up study in transgenic mice with sustained high glucose uptake and utilization in the heart by cardiac-specific overexpression of the insulin-independent glucose transporter GLUT1 (GLUT1-TG). Compared with wild-type litter mates, the GLUT1-TG mice showed a normal survival rate and unaltered contractile function of the heart monitored by serial echocardiography and by pressure-volume studies in isolated perfused hearts in the 2-year period. Furthermore, when hearts were subjected to ischemia-reperfusion, cardiac function of young and old GLUT1-TG recovered to the same level (86% and 83%, respectively) and exceeded that of both young and old wild-type hearts (52% and 35%, respectively; P<0.05). Nuclear magnetic resonance spectroscopic measurements with 31P showed delayed ATP depletion, reduced acidosis during ischemia, and improved recovery of high-energy phosphate content in old GLUT1-TG hearts (P<0.05 versus old wild-type). During reperfusion, glucose oxidation was 3-fold higher and fatty acid oxidation was 45% lower in old GLUT1-TG hearts compared with old wild-type (P<0.05), which suggests that the deleterious effects of excessive fatty acid oxidation during reperfusion was prevented in old GLUT1-TG hearts. CONCLUSIONS: We have demonstrated that a normal heart is able to adapt to long-term increases in basal glucose entry into cardiomyocytes without development of glucotoxicity. Furthermore, life-long increases in glucose uptake result in a favorable metabolic phenotype that affords protections against aging-associated increase of susceptibility to ischemic injury. |
