Hällsten K, Virtanen K A, Lönnqvist F, Janatuinen T, Turiceanu M, Rönnemaa T, Viikari J, Lehtimäki T, Knuuti J, Nuutila P
Turku PET Centre, University of Turku, Finland.
Diabet Med. 2004 Dec;21(12):1280-7. doi: 10.1111/j.1464-5491.2004.01332.x.
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.
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 [(18)F]-2-fluoro-2-deoxy-D-glucose ([(18)F]FDG) and positron emission tomography (PET) during euglycaemic hyperinsulinaemia before and after the treatment.
Rosiglitazone increased insulin-stimulated myocardial glucose uptake by 38% (from 38.7 +/- 3.4 to 53.3 +/- 3.6 micromol 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).
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.
过氧化物酶体增殖物激活受体γ（PPARγ）激活剂最近被确定为细胞增殖、炎症反应以及脂质和葡萄糖代谢的调节因子。这些药物可预防冠状动脉粥样硬化，并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研究结果背后的机制之一。本研究的目的是调查罗格列酮对2型糖尿病患者心肌葡萄糖摄取的影响。使用安慰剂和二甲双胍作为对照治疗。
在一项为期26周的双盲试验中，44例患者被随机分配接受罗格列酮（4mg，每日两次）、二甲双胍（1g，每日两次）或安慰剂治疗。在治疗前后的正常血糖高胰岛素血症期间，使用[（18）F]-2-氟-2-脱氧-D-葡萄糖（[（18）F]FDG）和正电子发射断层扫描（PET）测量心肌葡萄糖摄取。
罗格列酮使胰岛素刺激的心肌葡萄糖摄取增加38%（从38.7±3.4增加到53.3±3.6μmol 100g（-1）min（-1），P = 0.004），全身葡萄糖摄取增加36%（P = 0.01），而二甲双胍治疗对心肌（40.5±3.5对36.6±5.2，无显著性差异）或全身葡萄糖摄取无显著影响。各组间由速率-压力乘积确定的心肌作功相似。两种治疗对空腹血清游离脂肪酸（FFA）均无显著影响，但罗格列酮组在高胰岛素血症期间的FFA水平被更显著抑制（-47%，P = 0.02）。在汇总数据中，治疗期前后心肌葡萄糖摄取均与FFA浓度呈负相关（治疗前r = -0.54，P = 0.002；治疗后r = -0.43，P = 0.0
