Tschritter Otto, Hennige Anita M, Preissl Hubert, Porubska Katarina, Schäfer Silke A, Lutzenberger Werner, Machicao Fausto, Birbaumer Niels, Fritsche Andreas, Häring Hans-Ulrich
Department of Internal Medicine IV, University of Tübingen, Tübingen, Germany.
PLoS One. 2007 Nov 21;2(11):e1196. doi: 10.1371/journal.pone.0001196.
Insulin stimulates cerebrocortical beta and theta activity in lean humans. This effect is reduced in obese individuals indicating cerebrocortical insulin resistance. In the present study we tested whether insulin detemir is a suitable tool to restore the cerebral insulin response in overweight humans. This approach is based on studies in mice where we could recently demonstrate increased brain tissue concentrations of insulin and increased insulin signaling in the hypothalamus and cerebral cortex following peripheral injection of insulin detemir.
METHODOLOGY/PRINCIPAL FINDINGS: We studied activity of the cerebral cortex using magnetoencephalography in 12 lean and 34 overweight non-diabetic humans during a 2-step hyperinsulinemic euglycemic clamp (each step 90 min) with human insulin (HI) and saline infusion (S). In 10 overweight subjects we additionally performed the euglycemic clamp with insulin detemir (D). While human insulin administration did not change cerebrocortical activity relative to saline (p = 0.90) in overweight subjects, beta activity increased during D administration (basal 59+/-3 fT, 1(st) step 62+/-3 fT, 2(nd) step 66+/-5, p = 0.001, D vs. HI). As under this condition glucose infusion rates were lower with D than with HI (p = 0.003), it can be excluded that the cerebral effect is the consequence of a systemic effect. The total effect of insulin detemir on beta activity was not different from the human insulin effect in lean subjects (p = 0.78).
CONCLUSIONS/SIGNIFICANCE: Despite cerebrocortical resistance to human insulin, insulin detemir increased beta activity in overweight human subjects similarly as human insulin in lean subjects. These data suggest that the decreased cerebral beta activity response in overweight subjects can be restored by insulin detemir.
胰岛素可刺激瘦人皮质脑区的β波和θ波活动。肥胖个体中这种效应减弱，提示存在皮质脑区胰岛素抵抗。在本研究中，我们测试了地特胰岛素是否是恢复超重人群脑胰岛素反应的合适工具。该方法基于对小鼠的研究，我们最近发现，外周注射地特胰岛素后，小鼠脑组织中的胰岛素浓度升高，下丘脑和大脑皮质中的胰岛素信号增强。
方法/主要发现：我们在12名瘦人和34名超重非糖尿病患者中，通过两步高胰岛素正常血糖钳夹试验（每步90分钟），分别输注人胰岛素（HI）和生理盐水（S），利用脑磁图研究大脑皮质的活动。在10名超重受试者中，我们还进行了地特胰岛素（D）的正常血糖钳夹试验。超重受试者中，与人胰岛素相比，输注生理盐水时皮质脑区活动无变化（p = 0.90），而输注地特胰岛素期间β波活动增加（基础值59±3 fT，第一步62±3 fT，第二步66±5，p = 0.001，D与HI相比）。由于在此条件下，地特胰岛素组的葡萄糖输注速率低于人胰岛素组（p = 0.003），因此可以排除脑效应是全身效应的结果。地特胰岛素对β波活动的总体效应与瘦人受试者中人胰岛素的效应无差异（p = 0.78）。
结论/意义：尽管皮质脑区对人胰岛素存在抵抗，但地特胰岛素在超重受试者中增加β波活动的效果与在瘦人受试者中使用人胰岛素相似。这些数据表明，地特胰岛素可恢复超重受试者中降低的脑β波活动反应。
