Weigle D S, Koerker D J, Goodner C J
Am J Physiol. 1985 Jun;248(6 Pt 1):E681-6. doi: 10.1152/ajpendo.1985.248.6.E681.
We have reported that in the physiological concentration range pulsatile glucagon delivery (6 pulses in 90 min) is a more effective stimulus of rat hepatocyte glucose production than is continuous infusion of the same amount of hormone (pulsatile EC50 = 186 +/- 41 pg/ml, continuous EC50 = 884 +/- 190 pg/ml). At supraphysiological glucagon concentrations, however, the maximal response to continuous glucagon infusion exceeds the response to pulses (241 +/- 14 vs. 140 +/- 11 mumol X G-1 X 90 min-1). In an effort to explain these observations we derived a model for the 90-min hepatocyte responses to pulsatile and continuous glucagon delivery based on the waveform of the hepatocyte response to a transient glucagon stimulus. The model demonstrated that the time constant for response decay was an important determinant of the relative efficacy of the two patterns of hormone delivery. For the observed decay constant value of 0.132 +/- 0.02 min-1 the model predicted the following dose-response parameters: pulsatile EC50 = 131 pg/ml, Rmax = 119 mumol X G-1 X 90 min-1, continuous EC50 = 656 pg/ml, Rmax = 272 mumol X G-1 X 90 min-1. The ability of a model based only on the kinetics of a single pulse to simulate the observed dose-response relationship suggests that pulsatile stimulation is intrinsically more effective than continuous hormonal stimulation.
我们曾报道，在生理浓度范围内，脉冲式胰高血糖素递送（90分钟内6次脉冲）比持续输注相同量的激素更能有效刺激大鼠肝细胞葡萄糖生成（脉冲式EC50 = 186 ± 41 pg/ml，持续式EC50 = 884 ± 190 pg/ml）。然而，在超生理浓度的胰高血糖素条件下，持续输注胰高血糖素的最大反应超过了脉冲式刺激的反应（241 ± 14对140 ± 11 μmol·G⁻¹·90 min⁻¹）。为了解释这些观察结果，我们基于肝细胞对瞬时胰高血糖素刺激的反应波形，推导了一个关于肝细胞对脉冲式和持续式胰高血糖素递送90分钟反应的模型。该模型表明，反应衰减的时间常数是两种激素递送模式相对效力的重要决定因素。对于观察到的0.132 ± 0.02 min⁻¹的衰减常数值，该模型预测了以下剂量 - 反应参数：脉冲式EC50 = 131 pg/ml，Rmax = 119 μmol·G⁻¹·90 min⁻¹，持续式EC50 = 656 pg/ml，Rmax = 272 μmol·G⁻¹·90 min⁻¹。一个仅基于单个脉冲动力学的模型能够模拟观察到的剂量 - 反应关系，这表明脉冲式刺激本质上比持续激素刺激更有效。
