Enhancement of insulin-stimulated myocardial glucose uptake in patients with Type 2 diabetes treated with rosiglitazone
Enhancement of insulin-stimulated myocardial glucose uptake in patients with Type 2 diabetes treated with rosiglitazone
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DOI：
10.1111/j.1464-5491.2004.01332.x
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发表时间：
2004-12-01
影响因子：
3.5
通讯作者：
Nuutila, P
中科院分区：
文献类型：
--
作者：
Hällsten, K;Virtanen, KA;Nuutila, P
过氧化物酶体增殖物激活受体γ（PPARgamma）激活剂最近被鉴定为细胞增殖、炎症反应以及脂质和葡萄糖代谢的调节剂。这些药物可预防冠状动脉硬化，改善心肌梗死后心力衰竭患者的左心室重塑和功能。心肌代谢状态的改善可能是这些发现背后的机制之一。本研究旨在探讨罗格列酮对2型糖尿病患者心肌葡萄糖摄取的影响。方法将44例患者随机分为罗格列酮组（4 mg，b.i.d.），二甲双胍（1 g b.i.d.）或安慰剂在一个26周的双盲试验。用[F-18]-2-氟-2-脱氧-D-葡萄糖测定心肌葡萄糖摄取结果罗格列酮可使胰岛素刺激的心肌葡萄糖摄取增加38%（P < 0.05），而胰岛素刺激的心肌葡萄糖摄取增加38%（P < 0.05）。（从38.7+/-3.4至53.3+/-3.6 mumol 100 g（-1）min（-1），P=0.004）和全身葡萄糖摄取减少36%（P=0.01），而二甲双胍治疗对心肌（40.5+/-3.5 vs. 36.6+/-5.2，NS）或全身葡萄糖摄取没有显著影响。由心率-压力-乘积确定的心肌作功在两组之间相似。两种治疗对空腹血清游离脂肪酸（FFA）均无显著影响，但罗格列酮组高胰岛素血症期间FFA水平受到更多抑制（-47%，P=0.02）。在合并数据中，治疗期前（r=-0.54，P=0.002）和治疗期后（r=-0.43，P=0.01），心肌葡萄糖摄取与FFA浓度呈负相关。结论罗格列酮治疗2型糖尿病患者，除能改善全身胰岛素敏感性外，还能增强胰岛素刺激的心肌葡萄糖摄取，这可能与罗格列酮抑制血清游离脂肪酸有关。
Aims Peroxisome proliferator-activated receptor gamma (PPARgamma) activators have recently been identified as regulators of cellular proliferation, inflammatory responses and lipid and glucose metabolism. These agents prevent coronary arteriosclerosis and improve left ventricular remodelling and function in heart failure after myocardial infarction. Improvement in myocardial metabolic state may be one of the mechanisms behind these findings. The aim of this study was to investigate the effects of rosiglitazone on myocardial glucose uptake in patients with Type 2 diabetes. Placebo and metformin were used as control treatments.Methods Forty-four patients were randomized to treatment with rosiglitazone (4 mg b.i.d.), metformin (1 g b.i.d.) or placebo in a 26-week double-blinded trial. Myocardial glucose uptake was measured using [F-18]-2-fluoro-2-deoxy-D-glucose ([F-18]FDG) and positron emission tomography (PET) during euglycaemic hyperinsulinaemia before and after the treatment.Results Rosiglitazone increased insulin-stimulated myocardial glucose uptake by 38% (from 38.7+/-3.4 to 53.3+/-3.6 mumol 100 g(-1) min(-1), P=0.004) and whole body glucose uptake by 36% (P=0.01), while metformin treatment had no significant effect on myocardial (40.5+/-3.5 vs. 36.6+/-5.2, NS) or whole body glucose uptake. Myocardial work as determined by the rate-pressure-product was similar between the groups. Neither treatment had any significant effect on fasting serum free fatty acids (FFA) but the FFA levels during hyperinsulinaemia were more suppressed in the rosiglitazone group (-47%, P=0.02). Myocardial glucose uptake correlated inversely to FFA concentrations both before (r=-0.54, P=0.002) and after (r=-0.43, P=0.01) the treatment period in the pooled data. Furthermore, the increase in myocardial glucose uptake correlated inversely with interleukin-6 (IL-6) concentrations (r=-0.58, P=0.03).Conclusions In addition to the improvement in whole body insulin sensitivity, rosiglitazone treatment enhances insulin stimulated myocardial glucose uptake in patients with Type 2 diabetes, most probably due to its suppression of the serum FFAs.