Akpan J O, Wright P H, Dulin W E
Diabete Metab. 1987 Apr;13(2):122-8.
Isolated normal rat islets were pre-incubated with Streptozotocin (STZ), N-methylnitrosourea (MNU) or alloxan for 5, 10, 30 or 60 minutes at 0 degree C or 37 degrees C, and then were washed and incubated at 37 degrees C for 60 minutes with glucose (16.7 mM). Suppression of the insulinotropic response to glucose during incubation required 10 minutes of pre-incubation with the nitrosoureas whose effects were directly related to concentration and were temperature dependent. The suppressive effects of both nitrosoureas could be reduced or abolished by simultaneous addition to the pre-incubation media of nicotinamide, 2-deoxyglucose or 3-0-methyl-glucose, but were unaffected by reduced glutathione, glucosamine, N-acetylglucosamine or mannoheptulose. Unlike the nitrosoureas, alloxan was B-cytotoxic at 0 degree C. The effect of alloxan at 0 degree C was blocked by glutathione but not by glucose. The evidence in this study is inconsistent with the concept that the glucose moiety of STZ promotes entry and action of this nitrosourea in pancreatic islet cells. Secondly, it shows that the immediate B-cytotoxic action of alloxan differ from that of STZ or MNU and is not abolished by decrease in temperature.
将分离出的正常大鼠胰岛与链脲佐菌素（STZ）、N-甲基亚硝基脲（MNU）或四氧嘧啶在0℃或37℃下预孵育5、10、30或60分钟，然后洗涤并在37℃下与葡萄糖（16.7 mM）孵育60分钟。在孵育期间，对葡萄糖促胰岛素反应的抑制需要用亚硝基脲预孵育10分钟，其作用与浓度直接相关且依赖于温度。通过在预孵育培养基中同时添加烟酰胺、2-脱氧葡萄糖或3-O-甲基葡萄糖，两种亚硝基脲的抑制作用均可降低或消除，但还原型谷胱甘肽、氨基葡萄糖、N-乙酰氨基葡萄糖或甘露庚酮糖对其无影响。与亚硝基脲不同，四氧嘧啶在0℃时具有β细胞毒性。四氧嘧啶在0℃时的作用可被谷胱甘肽阻断，但不能被葡萄糖阻断。本研究中的证据与STZ的葡萄糖部分促进该亚硝基脲进入胰岛细胞并在其中发挥作用的概念不一致。其次，它表明四氧嘧啶的即时β细胞毒性作用与STZ或MNU不同，且不会因温度降低而消除。
