Kizer J S, Vargas-Gordon M, Brendel K, Bressler R
J Clin Invest. 1970 Oct;49(10):1942-8. doi: 10.1172/JCI106413.
Glucose intolerance has been observed following diphenylhydantoin (DPH) intoxication. Because of this association between DPH and hyperglycemia, the effect of DPH on insulin release in vitro using preparations of isolated islets of Langerhans and pancreatic pieces was examined. In concentrations identical with those considered necessary for adequate anticonvulsant therapy in man, DPH markedly decreases the insulin secretory response of pancreatic pieces to methacholine, 1 mug/ml, tolbutamide, 250 mug/ml, and glucose, 200 mg/100 ml, without any demonstrable alteration in the oxidative conversion of glucose-1-(14)C or glucose-6-(14)C to (14)CO(2) by isolated islets. This DPH-induced inhibition of insulin secretion is not reversed by higher concentrations of glucose (600 mg/100 ml) or by increasing concentrations of extracellular calcium ion (4-6 mmoles/liter). 0.1 mM potassium and 10(-4) M ouabain, however, effectively restore the DPH-induced block of insulin secretion in pancreatic pieces. 60 mM potassium ion, on the other hand, not only restores the insulin secretory response to glucose (200 mg/100 ml) but results in an added stimulation of insulin secretion in the presence of DPH. In the presence of DPH, (22)Na accumulation by isolated islets is decreased by 26-40% as compared with controls. Such evidence is considered to indirectly support the postulate that the electrophysiological properties of DPH on the pancreas are due to a stimulation of the membrane sodium-potassium-magnesium ATPase.
苯妥英（DPH）中毒后可观察到葡萄糖耐量异常。鉴于DPH与高血糖之间的这种关联，研究了DPH对离体胰岛和胰腺组织胰岛素释放的体外作用。在与人体充分抗惊厥治疗所需浓度相同的情况下，DPH显著降低胰腺组织对1μg/ml乙酰甲胆碱、250μg/ml甲苯磺丁脲和200mg/100ml葡萄糖的胰岛素分泌反应，而离体胰岛将葡萄糖-1-（14）C或葡萄糖-6-（14）C氧化转化为（14）CO₂的过程未出现任何明显改变。这种由DPH诱导的胰岛素分泌抑制作用不会因更高浓度的葡萄糖（600mg/100ml）或细胞外钙离子浓度增加（4 - 6mmol/L）而逆转。然而，0.1mM钾离子和10⁻⁴M哇巴因可有效恢复DPH诱导的胰腺组织胰岛素分泌阻滞。另一方面，60mM钾离子不仅可恢复对葡萄糖（200mg/100ml）的胰岛素分泌反应，还会在存在DPH的情况下额外刺激胰岛素分泌。在存在DPH的情况下，离体胰岛对（22）Na的摄取与对照组相比减少了26% - 40%。这些证据被认为间接支持了以下假设，即DPH对胰腺的电生理特性是由于刺激了膜钠钾镁ATP酶。
