Grill V, Westberg M
Department of Endocrinology, Karolinska Hospital, Stockholm, Sweden.
Endocrinology. 1987 Dec;121(6):2171-6. doi: 10.1210/endo-121-6-2171.
The apparent toxicity of alloxan was compared in nondiabetic rats and rats made diabetic by injection with streptozotocin during neonatal life (STZ). In the perfused pancreas of nondiabetic rats, 1 mM alloxan rapidly but evanescently stimulated insulin secretion; this effect was followed by pronounced inhibition of the insulin response to 27 mM glucose (94% inhibition) or 1 mM 3-isobutyl-1-methylxanthine (76% inhibition). Conversely, in STZ-diabetic rats the stimulatory effect of alloxan was reduced to 22% of that elicited in nondiabetic rats. In further contrast, the inhibitory effect of alloxan exposure was abolished with regard to subsequent glucose-induced insulin secretion and attenuated with regard to 3-isobutyl-1-methylxanthine-induced insulin secretion. A relative insensitivity to alloxan was also seen in collagenase-isolated islets, where alloxan completely abolished glucose-induced insulin secretion in islets from nondiabetic rats, but only nonsignificantly reduced secretion (by 37%) in islets from STZ-diabetic rats. Insensitivity to glucose in STZ diabetic rats is associated with insensitivity to alloxan. This implies a common defect in the initial recognition site of glucose and alloxan.
比较了四氧嘧啶在非糖尿病大鼠和新生期注射链脲佐菌素（STZ）制成的糖尿病大鼠中的表观毒性。在非糖尿病大鼠的灌注胰腺中，1 mM四氧嘧啶迅速但短暂地刺激胰岛素分泌；此效应之后是对27 mM葡萄糖（抑制94%）或1 mM 3 - 异丁基 - 1 - 甲基黄嘌呤（抑制76%）的胰岛素反应受到明显抑制。相反，在STZ糖尿病大鼠中，四氧嘧啶的刺激作用降至非糖尿病大鼠所引发作用的22%。进一步对比发现，四氧嘧啶暴露对随后葡萄糖诱导的胰岛素分泌的抑制作用消失，对3 - 异丁基 - 1 - 甲基黄嘌呤诱导的胰岛素分泌的抑制作用减弱。在胶原酶分离的胰岛中也观察到对四氧嘧啶的相对不敏感性，四氧嘧啶完全消除了非糖尿病大鼠胰岛中葡萄糖诱导的胰岛素分泌，但仅使STZ糖尿病大鼠胰岛中的分泌无显著减少（减少37%）。STZ糖尿病大鼠对葡萄糖的不敏感性与对四氧嘧啶的不敏感性相关。这意味着葡萄糖和四氧嘧啶的初始识别位点存在共同缺陷。
