Insulin content and insulinogenesis by the perfused rat pancreas: effects of long term glucose stimulation.
Insulin content and insulinogenesis by the perfused rat pancreas: effects of long term glucose stimulation.
复制标题
灌注大鼠胰腺的胰岛素含量和胰岛素生成：长期葡萄糖刺激的影响。
作者：
Donald L. Curry
灌流胰腺的动态反应不同胰腺之间的喂养和禁食大鼠。胰岛素分泌显着较低的胰腺从禁食大鼠在第一个40分钟的灌注在葡萄糖水平为200和300毫克/分升。此后，从40-90分钟，胰岛素分泌是相似的胰腺喂养和禁食大鼠。在禁食大鼠胰腺中观察到典型的双相胰岛素分泌曲线，包括短暂的胰岛素分泌峰，随后是缓慢上升的分泌相。相反，从第一阶段到第二阶段分泌的过渡加速胰腺喂养大鼠。这表明，细胞内胰岛素储存的转运可能会加剧，因为事实上，胰岛素的网站（如高尔基体）在胰腺喂养大鼠可能是完全启动的最佳分泌。总胰腺胰岛素测量支持这一概念。在进食和禁食24小时条件下，在不同时间的灌注（0，60，90分钟和6小时）和响应于不同的葡萄糖水平（0，200，300 mg/dl）后，测定总胰腺胰岛素含量。与进食大鼠的胰腺相比，禁食导致零时间胰岛素含量显著降低（39.2 +/- 2.4 vs. 61.6 +/- 9.8微克）。在喂食的大鼠胰腺中，300 mg/dl的葡萄糖刺激60分钟后，总胰岛素含量略有下降，但90分钟后恢复到基础水平，并在6小时的灌注期间保持在该水平。在禁食状态下，胰岛素含量作为时间的函数保持不变，直到60分钟，但增加了90分钟，相当于在胰腺喂养大鼠的水平。对低水平葡萄糖刺激的反应与对更高葡萄糖剂量的反应相比，来自进食和禁食大鼠的胰腺对葡萄糖（200 mg/dl）的反应在性质上相似（300毫克/分升），除了分泌较少。胰岛素含量保持相对恒定的灌注期长达60分钟。（定义为现有前胰岛素原和胰岛素原重新合成和转化为胰岛素，胰岛素的细胞内降解较少）作为葡萄糖浓度的函数而增加，并且作为动物的食物摄入的函数而在时间上不同。在用任何水平的葡萄糖刺激进行灌注的任何时间，胰岛素含量都没有超过来自喂食大鼠的胰腺中的零时间值。这表明胰岛素分泌是胰岛素生成的限速步骤。
The dynamic response of the perfused pancreas differed between pancreases from fed and fasted rats. Insulin secretion was significantly lower in pancreases from fasted rats during the first 40 min of perfusion at glucose levels of 200 and 300 mg/dl. Thereafter, from 40-90 min, insulin secretion was similar by pancreases from both fed and fasted rats. The typical biphasic insulin secretory profile, consisting of a transient spike of insulin secretion followed by a slowly rising secretory phase, was observed in pancreases from fasted rats. In contrast, the transition from first to second phase secretion was accelerated in pancreases from fed rats. This suggests that transport of intracellular insulin stores may be accentuated due to the fact that insulinogenic sites (e.g. Golgi) in pancreases from fed rats may be fully primed for optimal secretion. Total pancreatic insulin measurements support this concept. Total pancreatic insulin content was determined under fed and 24-h fasted conditions after various times of perfusion (0, 60, and 90 min and 6 h) and in response to various glucose levels (0, 200, and 300 mg/dl). Fasting resulted in a significant decrease in insulin content at zero time compared with pancreases from fed rats (39.2 +/- 2.4 vs. 61.6 +/- 9.8 micrograms). In the fed rat pancreases, total insulin content decreased slightly after a 60-min glucose stimulus of 300 mg/dl, but returned to the basal level after 90 min and remained at that level during a 6-h period of perfusion. In the fasted state, insulin content remained constant as a function of time until 60 min, but increased by 90 min to a level comparable to that in pancreases from fed rats. The response to lower levels of glucose stimulation (200 mg/dl) was qualitatively similar by pancreases from fed and fasted rats compared to the response to a higher glucose dose (300 mg/dl), except that secretion was less. Insulin content remained relatively constant for periods of perfusion up to 60 min. Insulinogenesis (defined as de novo synthesis and conversion of existing preproinsulin and proinsulin to insulin, less intracellular degradation of insulin) was increased as a function of glucose concentration and differed temporally as a function of the food intake of the animal. At no time of perfusion with any level of glucose stimulation did the insulin content exceed the zero time value in pancreases from fed rats. This suggests that insulin secretion is the rate-limiting step for insulinogenesis.