Virtanen K A, Haaparanta M, Grönroos T, Bergman J, Solin O, Rouru J, Nuutila P, Huupponen R
Department of Pharmacology and Clinical Pharmacology, University of Turku, Turku, Finland.
Diabetes Obes Metab. 2002 Jan;4(1):60-8. doi: 10.1046/j.1463-1326.2002.00185.x.
Direct assessment of tissue metabolism in vivo is important to understand the pathogenesis of obesity. Labelled glucose analogues are potential candidates to be used for this purpose. The aim of this study was to compare the kinetics and metabolism of 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG) in obese (fa/fa) and lean (Fa/?) Zucker rat tissues with microdialysis, and the measurement of uptake and phosphorylation with or without insulin bolus injection.
Obese (n = 10) and lean (n = 11) anaesthetized rats underwent a microdialysis study after FDG-injection either with or without insulin stimulation. Microdialysis probes were inserted in the jugular vein, quadriceps muscle and liver. After 110 min, tissue [(18)F]-uptake and intracellular phosphorylation of FDG were studied in blood, liver, skeletal muscle, subcutaneous adipose tissue, intra-abdominal adipose tissue and hypothalamus.
When measured with microdialysis, insulin-enhanced FDG disappeared from the blood pool and interstitial space of skeletal muscle and liver more effectively in lean rather than in obese animals. Insulin-stimulated skeletal muscle and adipose tissue[(18)F]-uptake was impaired in obese Zucker rats compared with lean animals. Hypothalamic FDG uptake was six to sevenfold higher than in other measured tissues, but was attenuated in obese rats. In liver and in mesenteric fat, insulin-enhanced FDG phosphorylation in lean rats compared with obese animals.
Positron-emitting glucose analogue FDG, combined with microdialysis and tissue analysis, is a feasible method in studying glucose metabolism at the cellular level in animal studies.
直接评估体内组织代谢对于理解肥胖症的发病机制很重要。标记的葡萄糖类似物是用于此目的的潜在候选物。本研究的目的是通过微透析比较肥胖(fa/fa)和瘦(Fa/?) Zucker大鼠组织中2-[(18)F]氟-2-脱氧-D-葡萄糖(FDG)的动力学和代谢情况,并测量有无胰岛素推注时的摄取和磷酸化情况。
肥胖(n = 10)和瘦(n = 11)的麻醉大鼠在注射FDG后,无论有无胰岛素刺激,均进行微透析研究。将微透析探针插入颈静脉、股四头肌和肝脏。110分钟后,研究血液、肝脏、骨骼肌、皮下脂肪组织、腹腔内脂肪组织和下丘脑的组织[(18)F]摄取及FDG的细胞内磷酸化情况。
通过微透析测量时,胰岛素增强的FDG从瘦动物而非肥胖动物的骨骼肌和肝脏血池及组织间隙中消失得更有效。与瘦动物相比,肥胖Zucker大鼠中胰岛素刺激的骨骼肌和脂肪组织[(18)F]摄取受损。下丘脑的FDG摄取比其他测量组织高6至7倍,但在肥胖大鼠中有所减弱。在肝脏和肠系膜脂肪中,与肥胖动物相比,瘦大鼠中胰岛素增强的FDG磷酸化。
正电子发射葡萄糖类似物FDG与微透析和组织分析相结合,是动物研究中在细胞水平研究葡萄糖代谢的一种可行方法。