Luo S, Meier A H, Cincotta A H
Ergo Science Corporation, Charlestown, Mass 02129, USA.
Neuroendocrinology. 1998 Jul;68(1):1-10. doi: 10.1159/000054344.
We examined whether reductions in body fat stores and insulin resistance in Syrian hamsters induced by bromocriptine are associated with reductions in daily norepinephrine (NE) and serotonin activities as indicated by their extracellular metabolite levels in the ventromedial hypothalamus (VMH). High levels of these monoamines within the VMH have been suspected to induce obesity and insulin resistance. Microdialysate samples from the VMH of freely moving obese male hamsters (BW: 208 +/- 5 g) were collected hourly over a 25-hour period before bromocriptine treatment, during the first day of and after 2 weeks of bromocriptine treatment (800 microg/animal daily, i.p.), and body composition and glucose tolerance analyses were conducted before and after 2 weeks of treatments. The microdialysate samples were analyzed by HPLC for metabolites of serotonin: 5-hydroxy-indoleacetic acid (5-HIAA), NE: 3-methoxy-4-hydroxy-phenylglycol (MHPG), and dopamine: homovanillic acid (HVA). Bromocriptine treatment for 14 days significantly reduced body fat by 60% and areas under the glucose and insulin curves during a glucose tolerance test by 50 and 46%, respectively. Concurrently, extracellular VMH contents of 5-HIAA, MHPG, and HVA were reduced by 50, 29 and 66%, respectively (p < 0.05). Similarly, VMH 5-HIAA and MHPG contents were 48 and 44% less, respectively (p < 0.05), in naturally glucose-tolerant hamsters compared with naturally glucose-intolerant hamsters. Bromocriptine induced reductions of body fat, and improvements in glucose intolerance may result in part from its ability to decrease serotonin and NE activities in the VMH.
我们研究了溴隐亭诱导叙利亚仓鼠体脂储备减少和胰岛素抵抗降低是否与腹内侧下丘脑（VMH）细胞外代谢产物水平所显示的每日去甲肾上腺素（NE）和5-羟色胺活性降低相关。VMH内这些单胺水平过高被怀疑会诱发肥胖和胰岛素抵抗。在溴隐亭治疗前、治疗第一天以及治疗2周后（800微克/动物/天，腹腔注射）的25小时内，每小时收集自由活动的肥胖雄性仓鼠（体重：208±5克）VMH的微量透析液样本，并在治疗2周前后进行身体成分和葡萄糖耐量分析。微量透析液样本通过高效液相色谱法分析5-羟色胺的代谢产物：5-羟吲哚乙酸（5-HIAA）、NE：3-甲氧基-4-羟基苯乙二醇（MHPG）和多巴胺：高香草酸（HVA）。溴隐亭治疗14天可使体脂显著减少60%，葡萄糖耐量试验期间葡萄糖和胰岛素曲线下面积分别减少50%和46%。同时，VMH细胞外5-HIAA、MHPG和HVA含量分别降低了50%、29%和66%（p<0.05）。同样，与天然葡萄糖不耐受的仓鼠相比，天然葡萄糖耐受的仓鼠VMH中5-HIAA和MHPG含量分别低48%和44%（p<0.05）。溴隐亭诱导的体脂减少和葡萄糖不耐受改善可能部分归因于其降低VMH中5-羟色胺和NE活性的能力。
