糖原池和3',5'-环磷酸腺苷释放对胰高血糖素在体外对肝葡萄糖生成的短暂作用的贡献。

Contribution by the glycogen pool and adenosine 3',5'-monophosphate release to the evanescent effect of glucagon on hepatic glucose production in vitro.

作者信息

Komjati M, Breitenecker F, Bratusch-Marrain P, Gampe J, Vierhapper H, Troch I, Waldhäusl W

出版信息

Endocrinology. 1985 Mar;116(3):978-86. doi: 10.1210/endo-116-3-978.

Abstract

To elucidate in vitro the transience of glucagon-induced hepatic glucose release, the effects of glucagon on hepatic glucose production and cAMP release were evaluated in the isolated rat liver preparation perfused by a nonrecirculating system. Glucagon was added to the infusate in stepwise increasing concentrations at 0, 60, and 100 min to give final concentrations of 2.5 X 10(-11), 10(-9), and 5 X 10(-8) M, respectively. Glucagon at 2.5 X 10(-11) M caused cAMP release [basal (mean +/- SD), 11.2 +/- 3.0 pmol/(min X 100 g BW)] to rise rapidly and plateau at 23.3 +/- 7.0 pmol/(min X 100 g BW), whereas hepatic glucose production [basal, 3.7 +/- 1.6 mumol/(min X 100 g BW)] increased only transiently to a maximum of 15.3 +/- 3.1 mumol/(min X 100 g BW) and fell thereafter. The enhanced cAMP release during the consecutive glucagon infusion was accompanied by a transient rise in hepatic glucose production during the second, but not during a third, glucagon infusion. When 3-isobutyl-1-methylxanthine, a potent phosphodiesterase inhibitor, was added to the perfusion medium (0.5 mM), the cAMP response to 2.5 X 10(-11) M glucagon was enhanced [247 +/- 124 pmol/(min X 100 g BW)] as was hepatic glucose production (+ 21%; P less than 0.05). Further augmentation of the glucagon concentration was followed by an increase in hepatic cAMP, but not glucose, release. When glucagon infusion (2.5 X 10(-11) M) was repeated with a glucagon-free period of 30 min in between, no stimulation of cAMP and consecutive glucose release was found during the second period. However, when the second glucagon dose was increased to 10(-9) M, glucose and cAMP release were again stimulated to the same extent as in experiments with no glucagon-free period in between. We conclude that the size of the glycogen pool and the cAMP concentration directly modulate hepatic glucose production and are responsible for evanescent glucagon action. This mechanism can be described by computer simulation.

摘要

为了在体外阐明胰高血糖素诱导的肝葡萄糖释放的短暂性，在非循环系统灌注的离体大鼠肝脏制剂中评估了胰高血糖素对肝葡萄糖生成和cAMP释放的影响。在0、60和100分钟时，将胰高血糖素以逐步增加的浓度添加到输注液中，最终浓度分别为2.5×10⁻¹¹、10⁻⁹和5×10⁻⁸M。2.5×10⁻¹¹M的胰高血糖素导致cAMP释放[基础值（平均值±标准差），11.2±3.0 pmol/（分钟×100 g体重）]迅速上升，并在23.3±7.0 pmol/（分钟×100 g体重）达到平台期，而肝葡萄糖生成[基础值，3.7±1.6 μmol/（分钟×100 g体重）]仅短暂增加至最大值15.3±3.1 μmol/（分钟×100 g体重），随后下降。在连续输注胰高血糖素期间，cAMP释放增强伴随着第二次但不是第三次输注胰高血糖素期间肝葡萄糖生成的短暂上升。当将一种有效的磷酸二酯酶抑制剂3-异丁基-1-甲基黄嘌呤添加到灌注培养基中（0.5 mM）时，对2.5×10⁻¹¹M胰高血糖素的cAMP反应增强[247±124 pmol/（分钟×100 g体重）]，肝葡萄糖生成也增强（增加21%；P<0.05）。进一步增加胰高血糖素浓度会导致肝cAMP释放增加，但不会导致葡萄糖释放增加。当在两次胰高血糖素输注（2.5×10⁻¹¹M）之间间隔30分钟无胰高血糖素期重复输注时，在第二个期间未发现对cAMP和随后葡萄糖释放的刺激。然而，当第二次胰高血糖素剂量增加到10⁻⁹M时，葡萄糖和cAMP释放再次被刺激到与两次输注之间无无胰高血糖素期的实验中相同的程度。我们得出结论，糖原池的大小和cAMP浓度直接调节肝葡萄糖生成，并负责胰高血糖素的短暂作用。这种机制可以通过计算机模拟来描述。