Phosphodiesterase-3 inhibition augments the myocardial infarct size-limiting effects of exenatide in mice with type 2 diabetes.
Phosphodiesterase-3 inhibition augments the myocardial infarct size-limiting effects of exenatide in mice with type 2 diabetes.
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磷酸二酯酶 3 抑制增强了艾塞那肽对 2 型糖尿病小鼠的心肌梗死面积限制作用。
DOI：
10.1152/ajpheart.00609.2012
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Birnbaum, Yochai
中科院分区：
文献类型：
--
作者：
Ye, Hongmei;Perez-Polo, Jose R;Bajaj, M;eep;Birnbaum, Yochai
胰升糖素样肽(GLP)-1受体的激活增加了细胞内cAMP，PKA的下游激活。西洛他唑(CIL)是一种磷酸二酯酶-3抑制剂，可阻止cAMP降解。我们评估了CIL是否增强了艾塞那肽(EX)诱导的db/db小鼠心肌cAMP水平和PKA活性的增加，以及是否增强了EX对梗塞面积(IS)的限制作用。小鼠在手术前24小时口服CIL(10 mg/kg)或赋形剂(10 mg/kg)。在手术前1小时，给小鼠注射EX(1μg/kg sc)或赋形剂。另一些小鼠接受PKA抑制剂H-89单独或与CIL+EX一起接受治疗。小鼠冠状动脉结扎30min，再灌流24h。EX和CIL均能增加心肌cAMP水平和PKA活性。EX+CIL组的水平显著高于对照组。EX和CIL都减少了IS。在CIL+EX组中IS最小。H-89可完全阻断EX+CIL的IS限制作用。EX+CIL降低缺血再灌注后第10号染色体上的磷酸酶和张力蛋白同源物的表达，增加Akt和ERK1/2的磷酸化。这些作用可被H-89阻断。综上所述，EX和CIL对糖尿病小鼠的IS限制具有相加作用。这种相加效应与cAMP诱导的PKA激活有关，因为H-89阻断了CIL+EX的保护作用。
Glucagon-like peptide (GLP)-1 receptor activation increases intracellular cAMP with downstream activation of PKA. Cilostazol (CIL), a phosphodiesterase-3 inhibitor, prevents cAMP degradation. We assessed whether CIL amplifies the exenatide (EX)-induced increase in myocardial cAMP levels and PKA activity and augments the infarct size (IS)-limiting effects of EX in db/db mice. Mice fed a Western diet received oral CIL (10 mg/kg) or vehicle by oral gavage 24 h before surgery. One hour before surgery, mice received EX (1 μg/kg sc) or vehicle. Additional mice received H-89, a PKA inhibitor, alone or with CIL + EX. Mice underwent 30 min of coronary artery occlusion and 24 h of reperfusion. Both EX and CIL increased myocardial cAMP levels and PKA activity. Levels were significantly higher in the EX + CIL group. Both EX and CIL reduced IS. IS was the smallest in the CIL + EX group. H-89 completely blocked the IS-limiting effects of EX + CIL. EX + CIL decreased phosphatase and tensin homolog on chromosome 10 upregulation and increased Akt and ERK1/2 phosphorylation after ischemia-reperfusion. These effects were blocked by H-89. In conclusion, EX and CIL have additive effects on IS limitation in diabetic mice. The additive effects are related to cAMP-induced PKA activation, as H-89 blocked the protective effect of CIL + EX.
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影响因子：
7.7
作者：
Noyan-Ashraf MH;Momen MA;Ban K;Sadi AM;Zhou YQ;Riazi AM;Baggio LL;Henkelman RM;Husain M;Drucker DJ
通讯作者：
Drucker DJ
影响因子：
5.3
作者：
S. Y. Park;J. H. Lee;Ki Young Kim;Eun Kyoung Kim;S. Yun;C. Kim;W. Lee;K. Hong
通讯作者：
S. Y. Park;J. H. Lee;Ki Young Kim;Eun Kyoung Kim;S. Yun;C. Kim;W. Lee;K. Hong
影响因子：
2.2
作者：
Dokken, B. B.;La Bonte, L. R.;McDonagh, P. F.
通讯作者：
McDonagh, P. F.
DOI：
10.1152/ajpheart.00583.2005
发表时间：
2006-01-01
影响因子：
4.8
作者：
Greer, JJM;Ware, DP;Lefer, DJ
通讯作者：
Lefer, DJ
影响因子：
8.2
作者：
Anzawa, R;Bernard, M;Feuvray, D
通讯作者：
Feuvray, D