Iloprost infusion prevents the insulin-induced reduction in skeletal muscle microvascular blood volume but does not enhance peripheral glucose uptake in type 2 diabetic patients
Iloprost infusion prevents the insulin-induced reduction in skeletal muscle microvascular blood volume but does not enhance peripheral glucose uptake in type 2 diabetic patients
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DOI：
10.1111/dom.13410
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发表时间：
2018-11-01
影响因子：
5.8
通讯作者：
Serne, Erik H.
中科院分区：
文献类型：
--
作者：
Emanuel, Anna L.;de Clercq, Nicolien C.;Serne, Erik H.
目的：在2型糖尿病中，胰岛素诱导的肌肉灌注受损被认为是导致全身葡萄糖摄取减少的原因。在这项研究中，我们研究了伊洛前列素，一种稳定的前列环素类似物，对胰岛素诱导的肌毛细血管募集和全身葡萄糖摄取的影响。（年龄55 [46-69]岁; BMI 33.1 [31.0-39] kg/m2）接受了两次高胰岛素血症-正常血糖钳夹，一次同时输注低剂量伊洛前列素，另一次不同时输注。在钳夹前和钳夹过程中对股外侧肌进行超声造影。结果：与禁食状态相比，胰岛素输注可使骨骼肌微血管血容量（MBV）减少约50%（空腹，1.77.10（-4）[1.54.10（-5）-2.44.10（-3）]任意单位（Au）;高胰岛素血症，6.69.10（-5）[2.68.10（-6）-5.72.10（-4）] Au; P = 0.050）。输注伊洛前列素可防止胰岛素诱导的骨骼肌毛细血管募集减少，在不加伊洛前列素和加伊洛前列素的条件下分别为（-49.5 [-89.5至55.3] %）至（8.0 [-68.8至306.6] %）。在输注伊洛前列素期间，葡萄糖消失率（R-d）没有显著变化（17.3 [10.0-40.8] μ mol/kg/min），与单独胰岛素输注相比（17.6 [9.9-68.7] μ mol/kg/min）。我们的数据表明胰岛素的急性改善-刺激的肌肉灌注不是绕过2型糖尿病中对葡萄糖摄取的细胞抗性的有吸引力的治疗方法。胰岛素诱导的肌肉灌注的长期改善是否有利于葡萄糖的处理仍有待确定。
Aims: In type 2 diabetes impaired insulin-induced muscle perfusion is thought to contribute to reduced whole-body glucose uptake. In this study, we examined the effects of iloprost, a stable prostacyclin analogue, on insulin-induced muscle capillary recruitment and whole-body glucose uptake.Materials and Methods: In a randomized cross-over design, 12 type 2 diabetes patients (age, 55 [46-69] years; BMI, 33.1 [31.0-39] kg/m(2)) underwent two hyperinsulinaemic-euglycaemic clamps, one with and one without simultaneous low-dose iloprost infusion. Contrast-enhanced ultrasonography of the vastus lateralis muscle was performed before and during the clamp. Muscle capillary recruitment was calculated as percentage change in microvascular blood volume (MBV) before and during the clamp.Results: Insulin infusion reduced skeletal muscle MBV by similar to 50% compared to the fasting state (fasting, 1.77.10(-4) [1.54.10(-5)-2.44.10(-3)] arbitrary units (AU); hyperinsulinaemia, 6.69.10(-5) [2.68.10(-6)-5.72.10(-4)] AU; P = 0.050). Infusion of iloprost prevented this insulin-induced skeletal muscle capillary derecruitment, from (-49.5 [-89.5 to 55.3] %) to (8.0 [-68.8 to 306.6] %), for conditions without and with iloprost, respectively. The rate of glucose disappearance (R-d) did not change significantly during iloprost infusion (17.3 [10.0-40.8] mu mol/kg/min) compared with insulin infusion alone (17.6 [9.9-68.7] mu mol/kg/min).Conclusions: Our data suggest that acute improvement in insulin-stimulated muscle perfusion is not an attractive therapeutic approach to bypass cellular resistance to glucose uptake in type 2 diabetes. Whether long-term improvements in insulin-induced muscle perfusion may prove beneficial for glucose disposal remains to be determined.