Grill V, Asplund K, Hellerström C, Cerasi E
Diabetes. 1975 Aug;24(8):746-52. doi: 10.2337/diab.24.8.746.
The (3H) cyclic AMP accumulation was measured in incubations of pancreatic islets from one-day, six-day, and thirty-five-day-old rats exposed to a low (0.6 mg./ml.) or a high (3.0 mg./ml.) glucose concentration with or without the addition of 0.1 mM. of the phosphodiesterase inhibitor 3-isobutyl- 1 -methylxanthine (IBMX). In the thirty-five-day-old rats, (3H) cyclic AMP accumulation was significantly enhanced after sixty minutes' incubation in a high glucose concentration and further increased by IBMX. These changes were paralleled by a stimulated insulin release, measured simultaneously. By contrast, in the one-day-old rats, no effect of glucose with or without IBMX was seen on (3H) cyclic AMP, while the minor insulin release due to high glucose alone was markedly potentiated by IBMX. Even in the presence of this agent the insulin response to glucose was, however, clearly inferior to that seen in the thirty-five-day-old animals. The stimulatory patterns of glucose-induced insulin release in the six-day-old animals was intermediate between the other two age groups. At this age, stimulation of (3H) cyclic AMP due to glucose was observed only in the presence of IBMX. Measurement of (3H) cyclic AMP after three minutes' incubation confirmed these different stimulatory patterns of glucose in the age groups studied. It is suggested that the inefficiency of glucose to stimulate the adenyl cyclase-cyclic AMP system of the beta cell from fetal and neonatal animals may be one important factor determining the insensitivity to the insulin-releasing action of glucose that exists at this stage of development.
在含有或不含有0.1 mM磷酸二酯酶抑制剂3 -异丁基- 1 -甲基黄嘌呤（IBMX）的情况下，将1日龄、6日龄和35日龄大鼠的胰岛分别置于低（0.6 mg/ml）或高（3.0 mg/ml）葡萄糖浓度中进行孵育，然后测定（3H）环磷酸腺苷（cAMP）的积累量。在35日龄大鼠中，在高葡萄糖浓度下孵育60分钟后，（3H）cAMP积累量显著增加，并且IBMX进一步增强了这种增加。同时测定发现，这些变化与胰岛素释放受到刺激相平行。相比之下，在1日龄大鼠中，无论有无IBMX存在，葡萄糖对（3H）cAMP均无影响，而仅高葡萄糖引起的少量胰岛素释放则被IBMX显著增强。然而，即使存在这种试剂，胰岛素对葡萄糖的反应仍明显低于35日龄动物。6日龄动物中葡萄糖诱导胰岛素释放的刺激模式介于其他两个年龄组之间。在这个年龄段，仅在存在IBMX的情况下才观察到葡萄糖对（3H）cAMP的刺激作用。孵育3分钟后对（3H）cAMP的测量证实了所研究年龄组中葡萄糖的这些不同刺激模式。有人提出，葡萄糖刺激胎儿和新生动物β细胞的腺苷酸环化酶 - 环磷酸腺苷系统效率低下，可能是决定在发育这个阶段对葡萄糖释放胰岛素作用不敏感的一个重要因素。
