Bromocriptine/SKF38393 treatment ameliorates obesity and associated metabolic dysfunctions in obese (ob/ob) mice.
Bromocriptine/SKF38393 treatment ameliorates obesity and associated metabolic dysfunctions in obese (ob/ob) mice.
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DOI：
10.1016/s0024-3205(97)00599-7
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发表时间：
1997-08-01
期刊：
影响因子：
6.1
通讯作者：
Scislowski, PWD
中科院分区：
文献类型：
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作者：
Cincotta, AH;Tozzo, E;Scislowski, PWD
据推测，多巴胺能活动是新陈代谢中枢调节系统的主要功能成分，可以被多巴胺调节药物所操纵。本研究旨在阐明药物多巴胺能激活在肥胖和糖尿病的代谢调节中的作用和重要性。我们用溴隐亭(多巴胺D-2激动剂)和SKF38393(多巴胺D-1激动剂)联合或单独用药治疗C57BL/6Job/ob小鼠2周，观察其对小鼠体成分、摄食量和血清代谢物的影响。溴隐亭和SKF38393分别在肥胖、高血糖和高胰岛素血症方面产生了适度的改善。然而，溴隐亭与SKF38393的组合导致体重(7.5g)、体脂(40%)、食物消耗(42%)以及血清葡萄糖(59%)、甘油三酯(37%)、游离脂肪酸(45%)和胰岛素(49%)浓度显著降低，而蛋白质质量(8%)增加。这些结果表明ob/ob小鼠体内代谢的调节成分受到多巴胺能活动的调节和/或由其组成。重要的是，多巴胺能D-1/D-2受体共激活最大限度地提高了这些小鼠的多巴胺能反应(即，改善代谢异常)。
It has been postulated that dopaminergic activities comprise a major functional component of a central regulatory system for metabolism which can be manipulated by dopamine modulating drugs. The present study is aimed at delineating the role and importance of pharmacological dopaminergic activation in the regulation of metabolism during obesity and diabetes. We treated C57BL/6J ob/ob mice for 2 weeks with bromocriptine (dopamine D-2 agonist), SKF38393 (dopamine D-1 agonist), both drugs combined or vehicle and monitored the effects of such treatment on body composition, food consumption, and serum metabolites. Bromocriptine and SKF38393 individually produced moderate improvements in obesity, hyperglycemia, and hyperinsulinemia. However, a combination of bromocriptine plus SKF38393 resulted in major reductions in body weight (7.5g), body fat (40%), food consumption (42%), and serum concentrations of glucose (59%), triglyceride (37%), free fatty acid (45%) and insulin (49%) while increasing protein mass (8%). These results indicate that regulatory components of metabolism in the ob/ob mouse are modulated by and/or are comprised of dopaminergic activities. Importantly, dopaminergic D-1/D-2 receptor coactivation maximizes this dopaminergic response (i.e., improvement of metabolic abnormalities) in these mice.