米力农诱导的胰岛素抵抗对大鼠糖脂代谢的影响

米力农诱导的胰岛素抵抗对大鼠糖脂代谢的影响

李伶^*, 杨刚毅

重庆医科大学检验系临床生化教研室, 重庆 400016

收稿日期:2002-09-17 修回日期:2003-08-10 出版日期:2003-09-15 发布日期:2003-09-15
通讯作者: 李伶*

Effect of Milrinone Induced Insulin Resistance on Glucose and Lipid Metabolism in Rats

LI Ling^*, YANG Gang-yi

Department of Clinical Biochemistry, Chongqing Medical University, Chongqing 400016, China

Received:2002-09-17 Revised:2003-08-10 Online:2003-09-15 Published:2003-09-15
Contact: LI Ling*

摘要/Abstract

摘要： 目的探讨选择性磷酸二酯酶Ⅲ(PhosphdiesteraseⅢ,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(free fatty acid,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(1,5,25μmoL·kg^-1)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.在意识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120 min时分别经导管给予米力农(25μmoL·kg^-1)和25%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2 min,各组FFA升高的百分数为:50%、52%、55%(1,5,25μmoL·kg^-1).在(5,25μmoL·kg^-1)组血浆胰岛素水平也明显高于对照组和给药前,仅25μmoL·kg^-1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(173±15 vs 634±87μmoL·kg^-1),肝糖输出(HGP)也明显高于给药前(-5.1±3.1 vs 7.5±2.0 mg·kg^-1·min).葡萄糖输注率(Glucose infusion rate,GIR)明显低于对照组和给药前(约21%).结论米力农损害了胰岛素抑制脂解和肝糖输出的能力和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.

关键词: 米力农, 胰岛素钳夹, 胰岛素抵抗

Abstract: Aim To investigate the effects of milrinone (a selective phosphodiesterase Ⅲ inhibitor PDE3) on insulin secretion, blood glucose, plasma free fatty acids (FFA) and dose-response relationship, and assess possible effects of milrinone on glucose metabolism and insulin sensitivity in conscious rats. Methods The catheterized nonstressed rats were administered various doses of milrinone (1, 5, 25 μmoL·kg^-1) and were compared with controls. A hyperinsulinaemic-euglycaemic clamp was established in counscious rats, and milrinone(25 μmoL·kg^-1) and 25 % dimethyl sulfoxide (DMSO, as a control) were given at 120 min during hyperinsulinaemic-euglycaemic clamping. Glucose turnover was determind with by gas chromatograph mass spectrometer (GC-MS). Results After dosing, plasma FFA levels in 3 milrinone groups significantly increased, compared with the controls and before dosing. The percentages of elevation of FFA by the different milrinone doses were very similar, 50%, and 52%, 55% for 1, 5, and 25 μmoL·kg^-1, repectively, at 2 min after dosing. Plasma insulin levels were significantly elevated in the 5 and 25 μmoL·kg^-1 groups, and the effect of milrione on glucose concentration was detectable only in 25 μ moL·kg^-1 group. During hyperinsulinaemic clamping, there were significant increase, in plasma FFA (from 173±15 to 634±87 μmoL·L^-1) and hepatic glucose production (HGP), and a significant decrease in glucose infusion rates (GIR) to about 21% and a slight increase in plasma insulin after milrinone treatment. Conclusion Milrinone impaires the ability of insulin to suppress lipolysis and HGP, and insulin-mediated glucose utilization in peripheral tissue. Therefore, milrinone administration may induce an acute insulin resistance in vivo.

Key words: milrinone, milrinone, insulin clamp, insulin clamp, insulin resistance, insulin resistance

中图分类号:

R963

R977.1

Supporting: Foundation item: National Natural Science Foundation of China (30270631) and Chongqing Board (99-3002) of Health and Chongqing Council of Science (02-34).
^*Corrsponding author. Tel.: 023-68486115

李伶^*, 杨刚毅. 米力农诱导的胰岛素抵抗对大鼠糖脂代谢的影响[J]. .

LI Ling^*, YANG Gang-yi. Effect of Milrinone Induced Insulin Resistance on Glucose and Lipid Metabolism in Rats[J]. .

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