Age-dependent changes in metabolism, contractile function, and ischemic sensitivity in hearts from db/db mice
Age-dependent changes in metabolism, contractile function, and ischemic sensitivity in hearts from db/db mice
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DOI：
10.2337/diabetes.52.2.434
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发表时间：
2003-02-01
期刊：
影响因子：
7.7
通讯作者：
Larsen, TS
中科院分区：
文献类型：
--
作者：
Aasum, E;Hafstad, AD;Larsen, TS
葡萄糖和棕榈酸酯代谢和收缩功能用来自6、10-12和16-18周龄的对照（db/+）和糖尿病（db/db）雌性小鼠的离体灌注工作心脏测量。棕榈酸氧化在6周龄db/db心脏中增加了2.2倍，并且在10- 12周龄和16- 18周龄心脏中保持升高。碳水化合物氧化在6周时是正常的，但在10-12周和16-18周时分别降低至对照组的27%和23%。在6周时，db/db心脏表现出机械功能的轻微降低，而在10-12周和16-18周时明显的功能障碍体征明显。在雄性小鼠心脏中检查缺血-再灌注后的机械功能;在6周时，db/db心脏显示正常恢复，而在12周时，其显著降低。脂肪酸氧化是再灌注后使用的主要底物。因此，糖尿病db/db心脏表现出进行性心肌病的体征;脂肪酸氧化增加先于碳水化合物氧化减少。在db/db心脏中，缺血后功能恢复减少，与含氧量正常的收缩性能的年龄依赖性变化平行。最后，过氧化物酶体增殖物激活受体-α治疗（3周）没有影响缺血再灌注的敏感性，即使碳水化合物氧化增加和棕榈酸氧化减少。
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.