| First Author | Aasum E | Year | 2003 |
| Journal | Diabetes | Volume | 52 |
| Issue | 2 | Pages | 434-41 |
| PubMed ID | 12540618 | Mgi Jnum | J:107138 |
| Mgi Id | MGI:3620339 | Doi | 10.2337/diabetes.52.2.434 |
| Citation | Aasum E, et al. (2003) Age-dependent changes in metabolism, contractile function, and ischemic sensitivity in hearts from db/db mice. Diabetes 52(2):434-41 |
| abstractText | Glucose and palmitate metabolism and contractile function were measured with ex vivo perfused working hearts from control (db/+) and diabetic (db/db) female mice at 6, 10-12, and 16-18 weeks of age. Palmitate oxidation was increased by 2.2-fold in 6-week-old db/db hearts and remained elevated in 10- to 12- and 16- to 18-week-old hearts. Carbohydrate oxidation was normal at 6 weeks but was reduced to 27 and 23% of control at 10-12 and 16-18 weeks, respectively. At 6 weeks, db/db hearts exhibited a slight reduction in mechanical function, whereas marked signs of dysfunction were evident at 10-12 and 16-18 weeks. Mechanical function after ischemia-reperfusion was examined in hearts from male mice; at 6 weeks, db/db hearts showed normal recovery, whereas at 12 weeks it was markedly reduced. Fatty acid oxidation was the predominant substrate used after reperfusion. Thus, diabetic db/db hearts exhibit signs of a progressive cardiomyopathy; increased fatty acid oxidation preceded reductions in carbohydrate oxidation. Postischemic recovery of function was reduced in db/db hearts, in parallel with age-dependent changes in normoxic contractile performance. Finally, peroxisome proliferator-activated receptor-alpha treatment (3 weeks) did not affect sensitivity to ischemia-reperfusion, even though carbohydrate oxidation was increased and palmitate oxidation was decreased. |
