Efendić S, Cerasi E, Luft R, Gladnikoff G
Diabetes. 1976 Oct;25(10):949-54. doi: 10.2337/diab.25.10.949.
Glucose, apart from its acute insulin-releasing effect, exerts a time-dependent potentiating action on subsequent stimulations of the pancreas. The influence of a 24-hour starvation on these two actions of glucose was studied with the completely isolated, perfused rat pancreas preparation. Starvation had no effect on the time kinetics of the insulin response, but the magnitudes of the early and late insulin-secretion phases were reduced to similar extents. It was demonstrated by using a wide glucose concentration range that the maximal insulin response is not significantly modified by starvation. In contrast, both the threshold of stimulation by and the Km for glucose were higher in the pancrease from fasted rats. Thus, starvation reduces the sensitivity of the islet for the insulin-releasing action of glucose. When the stimulatory concentrations of glucose were preceded for 40 minutes by the perfusion of 8.3 mM instead of the basal, 4.4 mM glucose, insulin secretion from the pancreas of fed animals was not modified. In contrast, raising the glucose concentration of the equilibrium period to 8.3 mM potentiated markedly the insulin response to subsequent stimulations in the pancreas from fasted rats. This potentiation expressed itself as increase in the maximal response: the Km for glucose was not reduced. Thus a 40-minute pretreatment with 8.3 mM glucose does not correct the diminished sensitivity induced by a 24-hour starvation. It is concluded that in starvation (1) the sensitivity for glucose of the mechanisms that initiate insulin release is diminished; (2) the sensitivity of the pancreas for the potentiation-inducing action of glucose is augumented. (3) In both respects, the insulin response of fasted rats is similar to that of mildly diabetic subjects. These and other findings suggest that the effect of glucose in initiation of insulin release and on generation of a state of potentiation in the islet are mediated by different mechanisms.
葡萄糖除了具有急性促胰岛素释放作用外，还对胰腺随后的刺激产生时间依赖性的增强作用。利用完全分离的灌注大鼠胰腺制备物，研究了24小时饥饿对葡萄糖这两种作用的影响。饥饿对胰岛素反应的时间动力学没有影响，但早期和晚期胰岛素分泌阶段的幅度均有类似程度的降低。通过使用广泛的葡萄糖浓度范围证明，饥饿不会显著改变最大胰岛素反应。相反，禁食大鼠胰腺中葡萄糖刺激的阈值和米氏常数（Km）均较高。因此，饥饿降低了胰岛对葡萄糖促胰岛素释放作用的敏感性。当用8.3 mM葡萄糖灌注40分钟而不是基础的4.4 mM葡萄糖作为刺激浓度之前，喂食动物胰腺的胰岛素分泌没有改变。相反，将平衡期的葡萄糖浓度提高到8.3 mM可显著增强禁食大鼠胰腺对随后刺激的胰岛素反应。这种增强表现为最大反应增加：葡萄糖的Km没有降低。因此，用8.3 mM葡萄糖预处理40分钟并不能纠正24小时饥饿引起的敏感性降低。得出的结论是，在饥饿状态下：（1）启动胰岛素释放机制对葡萄糖的敏感性降低；（2）胰腺对葡萄糖增强诱导作用的敏感性增强。（3）在这两个方面，禁食大鼠的胰岛素反应与轻度糖尿病患者相似。这些以及其他发现表明，葡萄糖在启动胰岛素释放和在胰岛中产生增强状态方面的作用是由不同机制介导的。
