Tang-Christensen M, Vrang N, Larsen P J
Department of Medical Anatomy, University of Copenhagen, Denmark.
Diabetes. 1998 Apr;47(4):530-7. doi: 10.2337/diabetes.47.4.530.
In the rat, the glucagon-like peptide 1 (GLP-1)(7-36) amide inhibits neurones in the central nervous system responsible for food and water intake. GLP-1-induced inhibition of food intake may involve the hypothalamic arcuate nucleus, whereas rostral sensory circumventricular organs may be responsible for the inhibitory action of GLP-1 on drinking. To further investigate the role of these blood-brain-barrier-free areas in GLP-1-induced inhibition of ingestive behavior, neonatal Wistar rats were subjected to monosodium glutamate (MSG) treatment, which causes extensive damage to the arcuate nucleus as well as to parts of the sensory circumventricular organs. The inhibitory effect of GLP-1 on feeding induced by food deprivation was completely abolished in MSG-lesioned rats. This effect was not due to either a loss of sensitivity to anorectic agents or a loss of taste aversion because MSG-treated animals displayed normal anorectic responses to central administration of corticotropin-releasing factor and normal aversive responses to peripheral administration of both lithium chloride and D-amphetamine. In non-lesioned rats, neuropeptide Y (NPY)-induced feeding was significantly reduced by concomitant GLP-1 administration. In contrast, GLP-1 had no effect on NPY-induced feeding in MSG-lesioned rats, suggesting that the GLP-1 receptors that mediate inhibition of feeding are localized upstream to the NPY-sensitive neurones inducing feeding behavior. The inhibitory effect of GLP-1 on water intake was tested using an ANG II-elicited drinking paradigm. Central administration of GLP-1 inhibited ANG II drinking in both MSG-treated rats and their nontreated littermates. In contrast, peripheral administration of GLP-1 did not inhibit ANG II-induced drinking behavior in MSG-treated rats. Thus it is evident that centrally acting GLP-1 modulates feeding and drinking behavior via neurones sensitive to MSG lesioning in the arcuate nucleus and circumventricular organs, respectively.
在大鼠中，胰高血糖素样肽1（GLP-1）（7-36）酰胺可抑制中枢神经系统中负责食物和水分摄入的神经元。GLP-1诱导的食物摄入抑制可能涉及下丘脑弓状核，而延髓感觉室周器官可能是GLP-1对饮水产生抑制作用的原因。为了进一步研究这些无血脑屏障区域在GLP-1诱导的摄食行为抑制中的作用，对新生Wistar大鼠进行了谷氨酸单钠（MSG）处理，该处理会对弓状核以及部分感觉室周器官造成广泛损伤。在MSG损伤的大鼠中，GLP-1对饥饿诱导的进食的抑制作用完全消失。这种效应既不是由于对厌食剂的敏感性丧失，也不是由于味觉厌恶丧失，因为MSG处理的动物对中枢给予促肾上腺皮质激素释放因子表现出正常的厌食反应，对外周给予氯化锂和D-苯丙胺均表现出正常的厌恶反应。在未损伤的大鼠中，同时给予GLP-1可显著减少神经肽Y（NPY）诱导的进食。相反，GLP-1对MSG损伤大鼠中NPY诱导的进食没有影响，这表明介导进食抑制的GLP-1受体位于诱导进食行为的NPY敏感神经元的上游。使用血管紧张素II诱导的饮水范式测试了GLP-1对水分摄入的抑制作用。中枢给予GLP-1可抑制MSG处理大鼠及其未处理的同窝仔鼠的血管紧张素II诱导的饮水。相反，外周给予GLP-1并未抑制MSG处理大鼠中血管紧张素II诱导的饮水行为。因此，很明显，中枢作用的GLP-1分别通过对弓状核和室周器官中MSG损伤敏感的神经元来调节进食和饮水行为。
