Department of Neuroendocrinology, University of Lübeck, Lübeck, Germany.
Diabetes. 2010 Apr;59(4):1101-7. doi: 10.2337/db09-1493. Epub 2010 Jan 12.
In the treatment of diabetic patients, the long-acting insulin analog insulin detemir is less prone to induce weight gain than other insulin formulations. Assuming that because of its pharmacologic properties, detemir displays stronger central nervous anorexigenic efficacy than human insulin, we compared acute effects of human insulin and detemir on electroencephalography (EEG) measures and food intake.
Frontocortical EEG direct current (DC) potentials were recorded in 15 healthy men during two hyperinsulinemic-euglycemic clamps that included an insulin bolus injection (human insulin, 17.75 mU/kg body wt; detemir, 90 mU/kg body wt) followed by a steady 90-min infusion (1.0 vs. 2.0 mU x kg(-1) x min(-1)). A higher dosage was chosen for detemir to compensate for its delay in impact relative to human insulin and to elicit similar systemic effects. At 20 min after infusion, subjects were allowed to eat ad libitum from a test buffet.
Mean glucose infusions to maintain euglycemia (P > 0.93) and blood glucose concentrations (P > 0.34) did not differ between conditions. Detemir infusion induced a negative DC-potential shift, averaging -372.2 microV from 21 to 90 min that was not observed during human insulin infusion (146.5 microV, P = 0.02). Detemir, in comparison with human insulin, reduced subsequent food intake by 303 kcal (1,257 vs. 1,560, P < 0.04).
While inducing comparable peripheral effects, detemir exerts stronger acute effects on brain functions than human insulin and triggers a relative decrease in food consumption, suggesting an enhanced anorexigenic impact of detemir compared with human insulin on central nervous networks that control nutrient uptake.
在治疗糖尿病患者时,长效胰岛素类似物地特胰岛素比其他胰岛素制剂不易引起体重增加。由于其药理学特性,我们假设地特胰岛素比人胰岛素显示出更强的中枢神经厌食作用,因此比较了人胰岛素和地特胰岛素对脑电图(EEG)测量和食物摄入的急性影响。
在两个高胰岛素-正常血糖钳夹中,15 名健康男性记录了额皮质直流电(DC)电位,其中包括胰岛素推注(人胰岛素,17.75 mU/kg 体重;地特胰岛素,90 mU/kg 体重),随后进行 90 分钟的稳定输注(1.0 与 2.0 mU x kg(-1) x min(-1))。选择更高剂量的地特胰岛素是为了补偿其相对于人胰岛素的延迟作用,并产生类似的全身效应。输注 20 分钟后,允许受试者从测试自助餐中自由进食。
维持血糖正常(P > 0.93)和血糖浓度(P > 0.34)的平均葡萄糖输注在两种情况下没有差异。地特胰岛素输注引起负的 DC 电位偏移,从 21 分钟到 90 分钟平均为-372.2 microV,而人胰岛素输注则没有观察到(146.5 microV,P = 0.02)。与人胰岛素相比,地特胰岛素使随后的食物摄入量减少了 303 卡路里(1,257 与 1,560,P < 0.04)。
虽然地特胰岛素和人胰岛素诱导相似的外周效应,但地特胰岛素对大脑功能的急性影响更强,并引发相对减少食物摄入,这表明与中枢神经系统控制营养摄取的网络相比,地特胰岛素对人胰岛素的厌食作用增强。