Giugliano D, Torella R, D'Onofrio F
Prostaglandins Med. 1981 Mar;6(3):283-97. doi: 10.1016/0161-4630(81)90152-x.
Experimental evidence has recently accumulated indicating that administration of some prostaglandins (PGs), particularly those of the E series, can evoke release of glucagon by the pancreatic alpha-cells. Virtually, all the in vitro studies (isolated perfused rat pancreas, isolated guinea-pig islets) agree that PGs can increase both basal and stimulated glucagon release. On the other hand, inhibition of PG synthesis with indomethacin blocks glucagon release. In rats and in normal humans, PGE1, but not PGA2 or PGF2a, causes a progressive rise of plasma glucagon levels. While in the rat this response seems independent of the adrenergic nervous system, in man the hyperglucagonemia induced by PGE1 is easily suppressed by propranolol, suggesting an interaction between the prostaglandin and the beta-receptors of the alpha-cell. Studies with inhibitors of PG synthesis in vivo have yielded conflicting results, depending on the particular experimental protocol used and on the type of inhibitor tested. In normal humans, it seems that acetylsalicylic acid (ASA) has no effect on glucagon response to arginine, tolbutamide and insulin-induced hypoglycemia. Conversely, a stimulator of PG synthesis, such as furosemide, increases glucagon response to an arginine pulse in man. In insulin-dependent diabetics, who present an exaggerated glucagon response to stimulants, ASA fails to alter glucagon response to arginine, but completely blunts the glucagon response to salbutamol, a weak beta-2 receptor agonist. In conclusion, these observations provide evidence in support to a role for PGs, at least PGE, in the contro of glucagon release.
最近积累的实验证据表明，给予某些前列腺素（PGs），尤其是E系列的前列腺素，可促使胰腺α细胞释放胰高血糖素。实际上，所有体外研究（离体灌注大鼠胰腺、离体豚鼠胰岛）均一致认为，PGs可增加基础和刺激状态下的胰高血糖素释放。另一方面，用吲哚美辛抑制PG合成可阻断胰高血糖素释放。在大鼠和正常人体内，PGE1可使血浆胰高血糖素水平逐渐升高，而PGA2或PGF2α则无此作用。虽然在大鼠中这种反应似乎与肾上腺素能神经系统无关，但在人体中，PGE1诱导的高胰高血糖素血症很容易被普萘洛尔抑制，这表明前列腺素与α细胞的β受体之间存在相互作用。体内使用PG合成抑制剂的研究结果相互矛盾，这取决于所采用的具体实验方案和所测试的抑制剂类型。在正常人体内，阿司匹林（ASA）似乎对胰高血糖素对精氨酸、甲苯磺丁脲和胰岛素诱导的低血糖的反应没有影响。相反，PG合成刺激剂，如呋塞米，可增加人体对精氨酸脉冲的胰高血糖素反应。在胰岛素依赖型糖尿病患者中，他们对刺激物的胰高血糖素反应过度，ASA未能改变胰高血糖素对精氨酸的反应，但完全减弱了胰高血糖素对沙丁胺醇（一种弱β2受体激动剂）的反应。总之，这些观察结果为PGs，至少是PGE，在胰高血糖素释放控制中的作用提供了支持证据。
