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目的 :探讨选择性磷酸二酯酶III(PDE3 )抑制剂米力农 (milrinone)对大鼠胰岛素分泌、血糖、血浆游离脂肪酸 (FFA)的影响和剂量依赖关系 ,及其在胰岛素钳夹状态下对大鼠糖代谢和胰岛素敏感性的影响。方法 :由植入导管给予大鼠不同剂量的米力农 ( 1、5、2 5 μmol/kg)在不同时相测定血糖、血浆FFA和胰岛素水平并与对照组比较。在清醒状态下建立大鼠高胰岛素 -正常血糖钳夹技术 ,并在钳夹 12 0min时分别经导管给予米力农 ( 2 5 μmol/kg)和 2 5 %二甲基亚砜 (DMSO ,对照组 )。采用气相色谱 -质谱仪 (GC -MS)测定糖代谢率。结果 :3个不同剂量米力农组血浆FFA浓度明显高于对照组和给药前 ,在注射后 2min ,各组FFA升高的百分数为 :5 0 %、5 2 %、5 5 % ( 1、5、2 5μmol/kg)。在 5、2 5 μmol/kg组血浆胰岛素水平也明显高于对照组和给药前 ,仅 2 5 μmol/kg组血糖浓度高于对照组和给药前。在胰岛素钳夹研究中 ,米力农处理组大鼠血浆FFA明显高于给药前 ,肝糖输出 (HGP)也明显高于给药前。葡萄糖输注率 (GIR)明显低于对照组和给药前。结论 :米力农损害了胰岛素抑制脂解和肝糖输出的能力及胰岛素介导的外周组织糖的利用。因此 ,米力农处理可能在体内诱导了一个急性胰岛素抵抗
AIM: To investigate the effect and dose-dependent relationship between milrinone, a selective inhibitor of phosphodiesterase III (PDE3), on insulin secretion, blood glucose and plasma free fatty acid (FFA) in rats. Effects on Glucose Metabolism and Insulin Sensitivity in Rats. Methods: The rats were implanted with different doses of Milrinone (1,5,2 5 μmol / kg) at different time points to measure blood glucose, plasma FFA and insulin levels compared with the control group. In the awake state, rats were given insulin - normal glucose clamp, and were administered with Milrinone (25 μmol / kg) and 25% dimethylsulfoxide (DMSO, group). The glucose metabolic rate was determined by gas chromatography-mass spectrometry (GC-MS). Results: The concentrations of FFA in three different doses of milrinone group were significantly higher than those in the control group and before administration. The percentage of increase of FFA in each group was 50%, 52%, 55% (1 , 5,25 μmol / kg). The level of plasma insulin in 5,2 5 μmol / kg group was also significantly higher than that in control group and before administration, and only 25 μmol / kg group had higher blood glucose levels than those in control group and before administration. In insulin clamp study, the plasma FFA of milrinone treatment group was significantly higher than before administration, and the hepatic glucose output (HGP) was also significantly higher than before administration. Glucose infusion rate (GIR) was significantly lower than the control group and before administration. CONCLUSION: Milrinone compromised insulin’s ability to inhibit lipolysis and glycogen output, as well as insulin-mediated peripheral tissue glucose utilization. Therefore, milrinone treatment may induce an acute insulin resistance in the body