CHRONIC INTRACEREBROVENTRICULAR INFUSION OF INSULIN REDUCES FOOD-INTAKE AND BODY-WEIGHT OF BABOONS
CHRONIC INTRACEREBROVENTRICULAR INFUSION OF INSULIN REDUCES FOOD-INTAKE AND BODY-WEIGHT OF BABOONS
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DOI：
10.1038/282503a0
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发表时间：
1979-01-01
期刊：
影响因子：
64.8
通讯作者：
PORTE, D
中科院分区：
文献类型：
--
作者：
WOODS, SC;LOTTER, EC;PORTE, D
身体肥胖通常保持在严格的限制1 -3。虽然尚不清楚这种调节是否符合严格的负反馈模式，但动物确实保持了相对恒定的身体肥胖。据推测，这种调节是由一些信号介导的，这些信号通知控制食物摄入的中心，可能位于大脑中，关于目前的肥胖状态5，6。该信号的身份尚不清楚，但身体肥胖与血浆中基础胰岛素水平之间的直接相关性7 -9表明胰岛素是可能的候选者。这种激素存在于许多物种的脑脊液（CSF）中10 -13，并且是血浆内水平随时间推移的缓慢积分14。因此，CSF中的胰岛素水平相对抵抗胰岛素的短期血浆波动。肥胖者的CSF胰岛素水平高于瘦对照组，并且肥胖者和瘦人的CSF胰岛素水平在长期禁食后均成比例降低15。因此，我们假设16，对身体肥胖作出反应的反馈系统使用CSF中的胰岛素浓度作为主要信号。在最近的报告中发现了对这种作用的额外支持，即胰岛素受体存在于大脑和脊髓的几个区域17 -20。我们现在为我们的假设提供了额外的证据，表明在狒狒中，将外源性胰岛素输注到CSF中会导致食物摄入量和体重的可靠和可预测的下降。
Body adiposity is normally maintained within rigid limits1–3. Although it is not clear that this regulation fits a strict negative feedback pattern, animals do maintain a relatively constant body adiposity4. It has been postulated that this regulation is mediated by some signal which informs centres controlling food intake, probably located in the brain, as to the present state of adiposity5,6. The identity of the signal is unknown, but the direct correlation between body adiposity and basal insulin levels in the plasma7–9, suggests insulin as a possible candidate. This hormone is present in the cerebrospinal fluid (CSF) of many species10–13, and is a slow integral over time of the level within the plasma14. Thus, the level of insulin in the CSF is relatively resistant to short-term plasma fluctuations of insulin. Obese humans have higher levels of CSF insulin than lean controls and the CSF insulin level of both obese and lean humans is reduced proportionately after a prolonged fast15. We have therefore postulated16that the feedback system responding to body adiposity uses the concentration of insulin in the CSF as a major signal. Additional support for such a role is found in recent reports that insulin receptors are present in several regions of the brain and spinal cord17–20. We now present additional evidence for our hypothesis by showing that in baboons the infusion of exogenous insulin into the CSF elicits a reliable and predictable decrease in food intake and body weight.