Sako Y, Wasada T, Umeda F, Ibayashi H
Metabolism. 1986 Oct;35(10):944-9. doi: 10.1016/0026-0495(86)90059-4.
The effect of glibenclamide, a sulfonylurea agent, on islet hormone secretion, particularly on glucagon was studied using isolated perifused pancreatic islets of normal and cysteamine-treated rats. In normal rat islets, glibenclamide enhanced both insulin and somatostatin release in normoglycemic (50 mg/dL) and glucopenic (0 mg/dL) states, as well as under the condition of arginine stimulation. In contrast, glibenclamide stimulated glucagon release only transiently, then suppressed it in a sustaining manner in each state. In the cysteamine-treated islets, as expected, somatostatin concentrations in the perifusate remained unchanged during the infusion of arginine and/or glibenclamide. Under this condition, glibenclamide enhanced insulin release to the same extent as seen in normal islets, and again markedly inhibited glucagon release. These observations indicate that in isolated perifused rat pancreatic islets, glibenclamide suppresses glucagon secretion independently of D cell stimulation. It is concluded that glibenclamide may exert its inhibitory effect directly on A cell rather than through paracrine action of concomitant somatostatin release, and that the suppression of glucagon secretion by glibenclamide may, in part, contribute to the antidiabetogenic effect of this compound.
使用正常大鼠和半胱胺处理大鼠的分离灌注胰腺胰岛，研究了磺脲类药物格列本脲对胰岛激素分泌，尤其是对胰高血糖素分泌的影响。在正常大鼠胰岛中，格列本脲在正常血糖（50mg/dL）和低血糖（0mg/dL）状态下以及在精氨酸刺激条件下均增强了胰岛素和生长抑素的释放。相比之下，格列本脲仅短暂刺激胰高血糖素释放，然后在每种状态下持续抑制其释放。在半胱胺处理的胰岛中，正如预期的那样，在灌注精氨酸和/或格列本脲期间，灌注液中的生长抑素浓度保持不变。在此条件下，格列本脲增强胰岛素释放的程度与正常胰岛中所见相同，并且再次显著抑制胰高血糖素释放。这些观察结果表明，在分离灌注的大鼠胰腺胰岛中，格列本脲独立于D细胞刺激而抑制胰高血糖素分泌。得出的结论是，格列本脲可能直接对A细胞发挥其抑制作用，而不是通过伴随生长抑素释放的旁分泌作用，并且格列本脲对胰高血糖素分泌的抑制作用可能部分有助于该化合物的抗糖尿病作用。
