Phosphodiesterase III Inhibition Increases cAMP Levels and Augments the Infarct Size Limiting Effect of a DPP-4 Inhibitor in Mice with Type-2 Diabetes Mellitus
机构：[1]The Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555, USA[2]The Section of Cardiology, Baylor College of Medicine, Houston, TX, USA[3]Texas Heart Institute, St. Luke Episcopal Hospital, Houston, TX, USA[4]Department of Anesthesiology, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China外科科室麻醉手术科（医技）昆明医科大学附属第一医院[5]Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China航天员中心[6]The Section of Endocrinology, Baylor College of Medicine, Houston, TX, USA
We assessed whether phosphodiesterase-III inhibition with cilostazol (Cil) augments the infarct size (IS)-limiting effects of MK0626 (MK), a dipeptidyl-peptidase-4 (DPP4) inhibitor, by increasing intracellular cAMP in mice with type-2 diabetes. Db/Db mice received 3-day MK (0, 1, 2 or 3 mg/kg/d) with or without Cil (15 mg/kg/d) by oral gavage and were subjected to 30 min coronary artery occlusion and 24 h reperfusion. Cil and MK at 2 and 3 mg/kg/d significantly reduced IS. Cil and MK had additive effects at all three MK doses. IS was the smallest in the MK-3+Cil. MK in a dose dependent manner and Cil increased cAMP levels (p < 0.001). cAMP levels were higher in the combination groups at all MK doses. MK-2 and Cil increased PKA activity when given alone; however, PKA activity was significantly higher in the MK-2+Cil group than in the other groups. Both MK-2 and Cil increased myocardial levels of Ser(133) P-CREB, Ser(523) P-5-lipoxygenase, Ser(473)P-Akt and Ser(633) P-eNOS. These levels were significantly higher in the MK-2+Cil group. Myocardial PTEN (Phosphatase and tensin homolog on chromosome ten) levels were significantly higher in the Db/Db mice compared to nondiabetic mice. MK-2 and Cil normalized PTEN levels. PTEN levels tended to be lower in the combination group than in the MK and Cil alone groups. MK and Cil have additive IS-limiting effects in diabetic mice. The additive effects are associated with an increase in myocardial cAMP levels and PKA activity with downstream phosphorylation of Akt, eNOS, 5-lipoxygenase and CREB and downregulation of PTEN expression.
第一作者机构：[1]The Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555, USA[2]The Section of Cardiology, Baylor College of Medicine, Houston, TX, USA[3]Texas Heart Institute, St. Luke Episcopal Hospital, Houston, TX, USA
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推荐引用方式(GB/T 7714)：
Birnbaum Yochai,Castillo Alexander C.,Qian Jinqiao,et al.Phosphodiesterase III Inhibition Increases cAMP Levels and Augments the Infarct Size Limiting Effect of a DPP-4 Inhibitor in Mice with Type-2 Diabetes Mellitus[J].CARDIOVASCULAR DRUGS AND THERAPY.2012,26(6):445-456.doi:10.1007/s10557-012-6409-x.
APA：
Birnbaum, Yochai,Castillo, Alexander C.,Qian, Jinqiao,Ling, Shukuan,Ye, Hongmei...&Ye, Yumei.(2012).Phosphodiesterase III Inhibition Increases cAMP Levels and Augments the Infarct Size Limiting Effect of a DPP-4 Inhibitor in Mice with Type-2 Diabetes Mellitus.CARDIOVASCULAR DRUGS AND THERAPY,26,(6)
MLA：
Birnbaum, Yochai,et al."Phosphodiesterase III Inhibition Increases cAMP Levels and Augments the Infarct Size Limiting Effect of a DPP-4 Inhibitor in Mice with Type-2 Diabetes Mellitus".CARDIOVASCULAR DRUGS AND THERAPY 26..6(2012):445-456
