Interleukin-1 beta-induced nitric oxide production from isolated rat islets is modulated by D-glucose and 3-isobutyl-1-methyl xanthine
Interleukin-1 beta-induced nitric oxide production from isolated rat islets is modulated by D-glucose and 3-isobutyl-1-methyl xanthine
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DOI：
10.1530/eje.0.1340251
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发表时间：
1996-02-01
影响因子：
5.8
通讯作者：
Nerup, J
中科院分区：
文献类型：
--
作者：
Andersen, HU;Mauricio, D;Nerup, J
已经提出白细胞介素-1 β通过诱导一氧化氮合成而引起选择性β细胞破坏。白细胞介素-1 β的细胞毒性作用受培养基中D-葡萄糖浓度的调节。本研究的目的是调查，如果D-葡萄糖介导的调制白细胞介素-1 β对胰岛素释放的影响，从离体大鼠胰岛相关的一氧化氮的生产调制。此外，我们希望研究增加细胞内cAMP浓度的试剂对白细胞介素-1 β诱导的亚硝酸盐产生的影响。我们证明D-葡萄糖增强大鼠胰岛中白细胞介素-1 β诱导的亚硝酸盐产生，而不影响诱导型一氧化氮合酶的mRNA水平。这种作用与白细胞介素-1 β对胰岛素释放的作用无关，因为在高胰岛素水平下发现白细胞介素-1 β对急性胰岛素释放的作用具有相对保护作用。（28 mmol/l）浓度的D-葡萄糖，并通过L-精氨酸类似物氨基胍阻断亚硝酸盐的产生，所述氨基胍选择性地抑制精氨酸诱导的一氧化氮合酶，没有导致对白细胞介素-1 β抑制作用的保护。无论是L-葡萄糖还是L-亮氨酸、甲苯磺丁脲和3-异丁基-1-甲基黄嘌呤都没有D-葡萄糖的增强作用。磷酸二酯酶抑制剂3-异丁基-1-甲基黄嘌呤在3.3 mmol/l D-葡萄糖下减少白细胞介素-1 β诱导的亚硝酸盐产生，这种作用可以通过cAMP类似物二丁酰cAMP再现。添加3-异丁基-1-甲基黄嘌呤导致白细胞介素-1 β诱导的诱导型一氧化氮合酶的mRNA水平降低三倍。我们的结论是白细胞介素-1 β诱导的胰岛一氧化氮合成增加D-葡萄糖，但不是由非底物促分泌素，和促分泌素，提高cAMP抑制胰岛一氧化氮的生产。
Interleukin-1 beta has been proposed to cause selective beta-cell destruction via the induction of nitric oxide synthesis. The cytotoxic effect of interleukin-1 beta is modulated by the concentration of D-glucose in the medium. The aim of this study was to investigate if D-glucose-mediated modulation of interleukin-1 beta effects on insulin release from isolated rat islets was related to modulation of nitric oxide production. Further, we wished to investigate the effects of agents increasing the intracellular concentration of cAMP on interleukin-1 beta-induced nitrite production, We demonstrated that D-glucose potentiated interleukin-1 beta-induced nitrite production in rat islets without affecting the mRNA level of the inducible nitric oxide synthase. This effect was dissociated from interleukin-1 beta action on insulin release, since a relative protection against interleukin-1 beta effects on acute insulin release was found at high (28 mmol/l) concentrations of D-glucose, and blocking nitrite production by the L-arginine analog aminoguanidine, which selectively inhibits the cytokine-inducible nitric oxide synthase, did not result in protection against the inhibitory action of interleukin-1 beta. Neither L-glucose nor the secretagogues L-leucine, tolbutamide and 3-isobutyl-1-methyl xanthine shared the potentiating effect of D-glucose. The phosphodiesterase inhibitor 3-isobutyl-l-methyl xanthine reduced interleukin-1 beta-induced nitrite production at 3.3 mmol/l D-glucose, an effect that could be reproduced by the cAMP analog dibutyryl cAMP. Addition of 3-isobutyl-l-methyl xanthine resulted in a threefold reduction in the mRNA level of interleukin-1 beta-induced inducible nitric oxide synthase. We conclude that interleukin-1 beta-induced islet nitric oxide synthesis is augmented by D-glucose, but not by non-substrate secretagogues, and that secretagogues that elevate cAMP inhibit islet nitric oxide production.