Dobbins R L, Davis S N, Neal D W, Cobelli C, Cherrington A D
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Am J Physiol. 1994 Mar;266(3 Pt 1):E467-78. doi: 10.1152/ajpendo.1994.266.3.E467.
The present study was designed to investigate if pulsatile hyperglucagonemia of physiological magnitude has greater efficacy in stimulating hepatic glucose production than constant glucagon. Paired studies were performed in conscious dogs. After insulin and glucagon were clamped at basal concentrations for 2 h, glucagon was elevated for 4 h with either a continuous infusion or pulses having physiological frequency and amplitude. With continuous infusion, plasma glucagon concentrations increased from 56 +/- 7 to 194 +/- 27 ng/l. With pulsatile infusion, glucagon concentrations started at 53 +/- 6 ng/l and then oscillated between 157 +/- 15 and 253 +/- 28 ng/l. Plasma insulin concentrations remained constant at basal levels. Glucose production was determined using a time-varying two-compartment model for glucose kinetics and deconvolution. After 15 min, glucose production had risen from 13.6 +/- 1.1 to 53.8 +/- 3.9 mumol.kg-1.min-1 with continuous infusion and from 12.9 +/- 0.6 to 50.6 +/- 2.9 mumol.kg-1.min-1 with pulsatile infusion. After 4 h, the production had fallen to 16.1 +/- 1.2 and 17.1 +/- 0.7 mumol.kg-1.min-1. In the present animal model with insulin held constant, no difference was noted between the response to continuous or pulsatile glucagon infusion.
本研究旨在调查生理幅度的脉冲式高胰高血糖素血症在刺激肝脏葡萄糖生成方面是否比持续的胰高血糖素具有更高的效力。在清醒犬身上进行配对研究。在将胰岛素和胰高血糖素钳制在基础浓度2小时后，通过持续输注或具有生理频率和幅度的脉冲使胰高血糖素升高4小时。持续输注时，血浆胰高血糖素浓度从56±7 ng/l增加到194±27 ng/l。脉冲式输注时，胰高血糖素浓度从53±6 ng/l开始，然后在157±15和253±28 ng/l之间振荡。血浆胰岛素浓度保持在基础水平不变。使用时变双室葡萄糖动力学模型和去卷积法测定葡萄糖生成。15分钟后，持续输注时葡萄糖生成从13.6±1.1上升至53.8±3.9 μmol·kg⁻¹·min⁻¹，脉冲式输注时从12.9±0.6上升至50.6±2.9 μmol·kg⁻¹·min⁻¹。4小时后，生成量降至16.1±1.2和17.1±0.7 μmol·kg⁻¹·min⁻¹。在本胰岛素保持恒定的动物模型中，持续或脉冲式输注胰高血糖素的反应之间未观察到差异。
