The in vitro inhibition of insulin secretion by diphenylhydantoin.
The in vitro inhibition of insulin secretion by diphenylhydantoin.
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二苯乙内酰脲对胰岛素分泌的体外抑制作用。
DOI：
10.1172/jci106413
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发表时间：
1970
期刊：
影响因子：
--
通讯作者：
R. Bressler
中科院分区：
文献类型：
--
作者：
J. Kizer;M. Vargas;K. Brendel;R. Bressler
葡萄糖耐受不良已被观察到后，二苯基海因（DPH）中毒。由于DPH和高血糖之间的这种关联，使用分离的胰岛和胰腺碎片的制备物在体外检测了DPH对胰岛素释放的影响。在与人类充分抗惊厥治疗所必需的浓度相同的浓度下，DPH显著降低胰腺碎片对乙酰甲胆碱（1 μ g/ml）、甲苯磺丁脲（250 μ g/ml）和葡萄糖（200 mg/100 ml）的胰岛素分泌反应，在分离的胰岛中葡萄糖-1-（14）C或葡萄糖-6-（14）C氧化转化为（14）CO（2）方面没有任何明显的改变。高浓度葡萄糖（600 mg/100 ml）或增加细胞外钙离子浓度（4-6 mmol/L）不能逆转这种由DPH诱导的胰岛素分泌抑制。0.1然而，10 mM钾和10（-4）M哇巴因有效地恢复了在胰腺碎片中由DPH诱导的胰岛素分泌阻断。另一方面，60 mM钾离子不仅恢复了对葡萄糖（200 mg/100 ml）的胰岛素分泌反应，而且在DPH存在下导致胰岛素分泌的额外刺激。在存在DPH的情况下，（22）与对照相比，分离的胰岛的Na积累减少了26-40%。这些证据被认为间接支持了DPH对胰腺的电生理特性是由于膜钠-钾-镁ATP酶的刺激的假设。
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.