Orosco M, Rouch C, Nicolaïdis S
Neurobiologie des Régulations, CNRS URA 1860, Collège de France, Paris.
Appetite. 1996 Feb;26(1):1-20. doi: 10.1006/appe.1996.0001.
We have shown previously that intravenous infusions of insulin, known to induce glucoprivic hunger, and of insulin combined with glucose, known to induce satiety, produce in the VMH and PVN of Wistar rats monoaminergic changes that differ from those related to spontaneously occurring hunger and satiety, while the genetically obese Zucker rat is totally resistant to the behavioural effects of insulin and insulin + glucose infusions. In the present study, the impact of these infusions on VMH and PVN monoamines in obese Zucker rats was assessed using microdialysis. Monaminergic changes (increase in DOPAC and 5-HIAA and decrease in DA and 5-HT) were quite similar in obese rats to those we found in normal rats when insulin was infused. In contrast, changes in 5-HT or DA in response to insulin and glucose were quite different in the Zucker rat. Monoaminergic changes related to meals were more dramatic in the Zucker rat and so were able to reverse the background changes produced by the insulin infusion. These data confirm the idea that the effect on monoamines of spontaneously occurring hunger and satiety is different from the effect on monoamines by insulin and glucose-induced hunger and satiety. The results show disturbances of the obese Zucker rat related both to insulin and to hypothalamic monoamines that may be involved in the hyperphagia and obesity of this model.
我们之前已经表明,静脉输注已知会诱发低血糖性饥饿的胰岛素以及已知会诱发饱腹感的胰岛素与葡萄糖的混合物,会在Wistar大鼠的腹内侧下丘脑(VMH)和室旁核(PVN)产生与自发产生的饥饿和饱腹感相关的单胺能变化不同的变化,而遗传性肥胖的Zucker大鼠对胰岛素和胰岛素+葡萄糖输注的行为效应完全有抗性。在本研究中,使用微透析评估了这些输注对肥胖Zucker大鼠VMH和PVN单胺的影响。当输注胰岛素时,肥胖大鼠的单胺能变化(3,4-二羟基苯乙酸(DOPAC)和5-羟吲哚乙酸(5-HIAA)增加,多巴胺(DA)和5-羟色胺(5-HT)减少)与我们在正常大鼠中发现的变化非常相似。相比之下,Zucker大鼠对胰岛素和葡萄糖反应时5-HT或DA的变化则大不相同。Zucker大鼠中与进食相关的单胺能变化更为显著,因此能够逆转胰岛素输注所产生的背景变化。这些数据证实了这样一种观点,即自发产生的饥饿和饱腹感对单胺的影响不同于胰岛素和葡萄糖诱导的饥饿和饱腹感对单胺的影响。结果显示肥胖的Zucker大鼠存在与胰岛素和下丘脑单胺相关的紊乱,这可能与该模型的食欲亢进和肥胖有关。