Glucose and insulin improve cardiac efficiency and postischemic functional recovery in perfused hearts from type 2 diabetic (db/db) mice
Glucose and insulin improve cardiac efficiency and postischemic functional recovery in perfused hearts from type 2 diabetic (db/db) mice
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DOI：
10.1152/ajpendo.00504.2006
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发表时间：
2007-05-01
影响因子：
5.1
通讯作者：
Aasum, Ellen
中科院分区：
文献类型：
--
作者：
Hafstad, Anne D.;Khalid, Ahmed M.;Aasum, Ellen
2型糖尿病（db/db）小鼠的心脏表现出底物利用的改变，脂肪酸氧化速率高，缺血后功能恢复减少，心脏效率降低。虽然db/db小鼠在体内表现出整体胰岛素抵抗，但我们最近报道，胰岛素诱导离体灌注db/db心脏中葡萄糖氧化的显著转变。我们推测，这种代谢的转变应该提高心脏效率，从而增加低流量缺血后的功能恢复。将db/db和非糖尿病（db/+）小鼠的心脏用0.7mM棕榈酸加5 mM葡萄糖（G）、5 mM葡萄糖和300 μ U/ml胰岛素（GI）或33 mM葡萄糖和900 μ U/ml胰岛素（HGHI）灌注。在db/+心脏中，底物氧化和缺血后恢复仅受到GI和HGHI的中度影响。相比之下，GI，特别是HGHI显着增加葡萄糖氧化和改善db/db心脏缺血后功能恢复。在HGHI存在下，db/db心脏的心脏效率显著改善，但在db/+心脏中没有改善。总之，胰岛素和葡萄糖使2型糖尿病小鼠心脏的心脏代谢正常化，恢复效率，并改善缺血后恢复。这些发现可能部分解释了葡萄糖-胰岛素-钾疗法对糖尿病心脏并发症患者的有益作用。
Hearts from type 2 diabetic (db/db) mice demonstrate altered substrate utilization with high rates of fatty acid oxidation, decreased functional recovery following ischemia, and reduced cardiac efficiency. Although db/db mice show overall insulin resistance in vivo, we recently reported that insulin induces a marked shift toward glucose oxidation in isolated perfused db/db hearts. We hypothesize that such a shift in metabolism should improve cardiac efficiency and consequently increase functional recovery following low-flow ischemia. Hearts from db/db and nondiabetic (db/+) mice were perfused with 0.7 mM palmitate plus either 5 mM glucose (G), 5 mM glucose and 300 mu U/ml insulin (GI), or 33 mM glucose and 900 mu U/ml insulin (HGHI). Substrate oxidation and postischemic recovery were only moderately affected by GI and HGHI in db/+ hearts. In contrast, GI and particularly HGHI markedly increased glucose oxidation and improved postischemic functional recovery in db/db hearts. Cardiac efficiency was significantly improved in db/db, but not in db/+ hearts, in the presence of HGHI. In conclusion, insulin and glucose normalize cardiac metabolism, restore efficiency, and improve postischemic recovery in type 2 diabetic mouse hearts. These findings may in part explain the beneficial effect of glucose-insulin-potassium therapy in diabetic patients with cardiac complications.