Weigle D S, Koerker D J, Goodner C J
Am J Physiol. 1984 Oct;247(4 Pt 1):E564-8. doi: 10.1152/ajpendo.1984.247.4.E564.
We have compared the effects of pulsatile and continuous glucagon administration on hepatocyte glucose production in order to clarify the physiological role of pulsatile hormone secretion. Two identical columns containing freshly isolated rat hepatocytes mixed with polyacrylamide gel beads were perifused with oxygenated tissue culture medium. A fixed total amount of glucagon was delivered to one column as a continuous 90-min infusion and to the other column as a series of six 3-min pulses. A 15-min interpulse interval was chosen in order to approximate the 10- to 12-min interval observed in primates while permitting the resolution of individual hepatocyte responses. With this protocol, the EC50 values for pulsatile and continuous glucagon administration were 186 +/- 41 and 884 +/- 190 (SD) pg/ml, respectively. For glucagon concentrations less than 1,000 pg/ml, pulsatile administration always led to greater hepatocyte glucose production than continuous administration (P = 0.008) and, in the dose range equivalent to concentrations in portal plasma, pulsed glucagon enhanced glucose production twofold. The data suggest that pulsatile secretion is the more efficient means for islet A cells to stimulate hepatic glucose production.
为了阐明脉冲式激素分泌的生理作用，我们比较了脉冲式和持续给予胰高血糖素对肝细胞葡萄糖生成的影响。将两根相同的柱子，里面装有新鲜分离的大鼠肝细胞与聚丙烯酰胺凝胶珠混合，用含氧的组织培养基进行灌流。将固定总量的胰高血糖素以连续90分钟输注的方式输送到一根柱子，以一系列6个3分钟脉冲的方式输送到另一根柱子。选择15分钟的脉冲间隔，以便接近在灵长类动物中观察到的10至12分钟间隔，同时能够分辨单个肝细胞的反应。按照此方案，脉冲式和持续给予胰高血糖素的EC50值分别为186±41和884±190（标准差）pg/ml。对于胰高血糖素浓度低于1000 pg/ml的情况，脉冲式给药总是比持续给药导致更高的肝细胞葡萄糖生成（P = 0.008），并且在相当于门静脉血浆浓度的剂量范围内，脉冲式胰高血糖素使葡萄糖生成增加两倍。数据表明，脉冲式分泌是胰岛A细胞刺激肝葡萄糖生成的更有效方式。
