Insulin and resveratrol act synergistically, preventing cardiac dysfunction in diabetes, but the advantage of resveratrol in diabetics with acute heart attack is antagonized by insulin
Insulin and resveratrol act synergistically, preventing cardiac dysfunction in diabetes, but the advantage of resveratrol in diabetics with acute heart attack is antagonized by insulin
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DOI：
10.1016/j.freeradbiomed.2010.08.032
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发表时间：
2010-12-01
影响因子：
7.4
通讯作者：
Hung, Li-Man
中科院分区：
文献类型：
--
作者：
Huang, Hung-Pang;Huang, Shiang-Suo;Hung, Li-Man
白藜芦醇(RSV)是一种具有心血管保护和胰岛素增敏作用的天然酚类化合物。本研究比较了白藜芦醇(RSV)及其与胰岛素合用对链脲佐菌素(STZ)诱导的糖尿病大鼠死亡率、血流动力学、胰岛素信号和亚硝化应激的影响。在常氧条件下，糖尿病大鼠心肌I/R损伤时，心脏收缩和舒缩功能及胰岛素介导的Akt/GLUT4(葡萄糖转运蛋白4)活性受损。在STZ糖尿病大鼠中，RSV和胰岛素的联合应用可显著预防上述糖尿病相关异常。糖尿病心肌I/R损伤后死亡率、诱导型一氧化氮合酶(INOS)/硝基酪氨酸蛋白表达和超氧阴离子生成也进一步增加。与单纯RSV治疗相比，RSV治疗可降低死亡率(从625%降至18%)，改善心脏收缩功能；抑制I/R损伤糖尿病心肌iNOS/硝基酪氨酸蛋白过度表达和超氧阴离子产生；联合治疗可显着改善胰岛素信号转导障碍和超氧阴离子产生，但对死亡率(30%)和心功能无明显改善。结果表明，胰岛素和RSV协同预防糖尿病患者的心功能障碍，这可能与激活胰岛素介导的Akt/GLUT4信号通路平行，尽管在胰岛素和RSV联合治疗中同时观察到保护信号(Akt/GLUT4)的激活和不利标志物(NOS、硝基酪氨酸和超氧阴离子)的抑制胰岛素抵消了合并急性心脏病发作的糖尿病患者RSV的优势(C)2010 Elsevier Inc.保留所有权利
Resveratrol (RSV) a natural phenolic compound has been found to display cardiovascular protective and insulin sensitizing properties In this study the effects of RSV and its combination with insulin on mortality hemodynamics insulin signaling and nitrosative stress were compared in streptozotocin (STZ) induced diabetic rats with or without acute myocardial ischemia/reperfusion (I/R) injury Under normoxic conditions cardiac systolic and diastolic functions and insulin-mediated Akt/GLUT4 (glucose transpoitel 4) activation were impaired in STZ diabetic lats The combination of RSV and insulin significantly prevented the above diabetes-associated abnormalities Notwithstanding that the diabetic state rendered the animals more susceptible to myocardial I/R injury and the mortality rate and inducible nitric oxide synthase (iNOS)/nitrotyrosine protein expression and superoxide anion production were also further increased in I/R injured diabetic hearts In contrast RSV treatment alone resulted in a lower mortality rate (from 625 to 18%) and better cardiac systolic function than its combination with insulin RSV also inhibited INOS/nitrotyrosine protein overexpression and superoxide anion overproduction in I/R injured diabetic myocardium Hyperglycemia impairment of insulin signaling overexpression of INOS/narotyrosine and superoxide anion overproduction were markedly rescued by the combination treatment which did not show an improvement in mortality rate (30%) or cardiac performance over RSV treatment alone These results indicate that insulin and RSV synergistically prevented cardiac dysfunction in diabetes and this may be in parallel with activation of the insulin mediated Akt/GLUT4 signaling pathway Although activation of the protective signal (Akt/GLUT4) and suppression of the adverse markers (NOS nitrotyrosine and superoxide anion) were simultaneously observed in insulin and RSV combination treatment insulin counteracted the advantage of RSV in diabetics with acute heart attack (C) 2010 Elsevier Inc All rights reserved