Boschmann Michael, Schroeder Christoph, Christensen Niels Juel, Tank Jens, Krupp Goetz, Biaggioni Italo, Klaus Susanne, Sharma Arya M, Luft Friedrich C, Jordan Jens
German Institute of Human Nutrition, 14558 Potsdam, Germany.
J Clin Endocrinol Metab. 2002 Nov;87(11):5130-7. doi: 10.1210/jc.2002-020533.
Genetic variability, numerous medications, and some illicit drugs influence norepinephrine transporter (NET) function; however, the metabolic consequences of NET inhibition are poorly understood. We performed a randomized, double-blind, cross-over trial in 15 healthy subjects who ingested 8 mg of the selective NET inhibitor reboxetine or placebo. Energy expenditure and substrate oxidation rates were determined by indirect calorimetry before and during iv infusion of 0.25, 0.5, 1, and 2 micro g isoproterenol/min. Adipose tissue metabolism was studied by microdialysis before and during local isoproterenol perfusion. At rest, energy expenditure and substrate oxidation rates did not differ between reboxetine and placebo treatment. At 1 micro g/min isoproterenol, energy expenditure was significantly increased in men (+15%) and women (+20%) with both reboxetine and placebo treatment. However, carbohydrate oxidation rate was significantly higher with reboxetine compared with placebo. Baseline and isoproterenol-stimulated adipose tissue blood flow was about 2-fold higher with reboxetine vs. placebo. Furthermore, glucose supply and metabolism was significantly increased and lipid mobilization much more stimulated in adipose tissue under reboxetine when compared with placebo at all isoproterenol concentrations used. We conclude that acute NET inhibition increases adipose tissue glucose uptake and metabolism. While lipid mobilization is increased, overall lipid oxidation is decreased during beta-adrenergic stimulation. This effect cannot be explained by increased systemic or adipose tissue norepinephrine concentrations. Instead, NET inhibition may sensitize adipose tissue to beta-adrenergic stimulation.
基因变异性、多种药物以及一些非法药物会影响去甲肾上腺素转运体（NET）的功能；然而，NET抑制的代谢后果却知之甚少。我们对15名健康受试者进行了一项随机、双盲、交叉试验，这些受试者分别摄入8毫克选择性NET抑制剂瑞波西汀或安慰剂。在静脉输注异丙肾上腺素的速率为0.25、0.5、1和2微克/分钟之前及期间，通过间接测热法测定能量消耗和底物氧化率。在局部灌注异丙肾上腺素之前及期间，通过微透析研究脂肪组织代谢。静息时，瑞波西汀治疗组和安慰剂治疗组的能量消耗和底物氧化率没有差异。在输注速率为1微克/分钟的异丙肾上腺素时，瑞波西汀治疗组和安慰剂治疗组的男性（增加15%）和女性（增加20%）的能量消耗均显著增加。然而，与安慰剂相比，瑞波西汀治疗组的碳水化合物氧化率显著更高。与安慰剂相比，瑞波西汀治疗组的基线和异丙肾上腺素刺激后的脂肪组织血流量高出约2倍。此外，在所有使用的异丙肾上腺素浓度下，与安慰剂相比，瑞波西汀治疗时脂肪组织中的葡萄糖供应和代谢显著增加，脂质动员受到的刺激更大。我们得出结论，急性NET抑制会增加脂肪组织对葡萄糖的摄取和代谢。虽然脂质动员增加，但在β-肾上腺素能刺激期间整体脂质氧化减少。这种效应无法用全身或脂肪组织去甲肾上腺素浓度增加来解释。相反，NET抑制可能使脂肪组织对β-肾上腺素能刺激更加敏感。
