Santuré Marta, Pitre Maryse, Nadeau André, Bachelard Hélène
Hypertension Research Unit and Diabetes Research Unit, Laval University Hospital Research Center, Ste-Foy, Quebec, Canada.
Metabolism. 2003 Aug;52(8):978-86. doi: 10.1016/s0026-0495(03)00110-0.
In rats, diets high in simple sugar induce insulin resistance and alter vascular reactivity. The present study was designed to evaluate the effects of 5 weeks treatment with troglitazone on insulin sensitivity, regional hemodynamics, and vascular responses to insulin in chow-fed and high-sucrose-fed rats. Male rats were randomly divided in 4 groups to receive a regular chow diet in the absence (group 1) or presence of troglitazone (0.2% in food; group 2), or a sucrose-enriched diet in the absence (group 3) or presence of troglitazone (group 4) for 5 weeks. The rats were instrumented with Doppler flow probes and intravascular catheters to determine blood pressure, heart rate, and regional blood flows. Insulin sensitivity was assessed by the euglycemic hyperinsulinemic clamp technique. Glucose transport activity was examined in isolated muscles. Sucrose feeding was found to induce insulin resistance and to impair the insulin-mediated skeletal muscle vasodilation. Treatment with troglitazone was found to increase whole-body insulin sensitivity in sucrose- and chow-fed rats, but had no effect on skeletal muscle glucose transport activity measured in isolated muscles from both dietary groups. Changes in regional hemodynamics were observed in both dietary cohorts treated with troglitazone, and the hindquarter vasoconstrictor response to insulin noted in sucrose-fed rats was abolished by the treatment. The vascular effects of troglitazone, and its insulin-related attenuating effects on contractile tone, could have contributed, in part, to improve insulin action on peripheral glucose disposal, presumably by improving blood flow distribution and glucose delivery.
在大鼠中，高糖饮食会诱发胰岛素抵抗并改变血管反应性。本研究旨在评估用曲格列酮治疗5周对正常饮食和高蔗糖饮食大鼠的胰岛素敏感性、局部血流动力学以及血管对胰岛素反应的影响。雄性大鼠被随机分为4组，分别在无曲格列酮（第1组）或有曲格列酮（食物中含0.2%；第2组）的情况下接受正常饮食，或者在无曲格列酮（第3组）或有曲格列酮（第4组）的情况下接受富含蔗糖的饮食，持续5周。给大鼠安装多普勒血流探头和血管内导管以测定血压、心率和局部血流量。通过正常血糖高胰岛素钳夹技术评估胰岛素敏感性。在分离的肌肉中检测葡萄糖转运活性。发现蔗糖喂养会诱发胰岛素抵抗并损害胰岛素介导的骨骼肌血管舒张。发现用曲格列酮治疗可提高蔗糖喂养和正常饮食大鼠的全身胰岛素敏感性，但对两个饮食组分离肌肉中测得的骨骼肌葡萄糖转运活性没有影响。在用曲格列酮治疗的两个饮食组中均观察到局部血流动力学的变化，并且治疗消除了蔗糖喂养大鼠中观察到的后肢对胰岛素的血管收缩反应。曲格列酮的血管作用及其对收缩张力的胰岛素相关减弱作用，可能部分有助于改善胰岛素对外周葡萄糖处置的作用，大概是通过改善血流分布和葡萄糖输送来实现的。
