NICOTINAMIDE PREVENTS INTERLEUKIN-1 EFFECTS ON ACCUMULATED INSULIN RELEASE AND NITRIC-OXIDE PRODUCTION IN RAT ISLETS OF LANGERHANS
NICOTINAMIDE PREVENTS INTERLEUKIN-1 EFFECTS ON ACCUMULATED INSULIN RELEASE AND NITRIC-OXIDE PRODUCTION IN RAT ISLETS OF LANGERHANS
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DOI：
10.2337/diabetes.43.6.770
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发表时间：
1994-06-01
期刊：
影响因子：
7.7
通讯作者：
NERUP, J
中科院分区：
文献类型：
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作者：
ANDERSEN, HU;JORGENSEN, KH;NERUP, J
烟酰胺（NA）可预防巨噬细胞和白细胞介素-1（IL-1）介导的体外β细胞损伤以及胰岛素依赖性糖尿病（IDDM）动物模型中的糖尿病发展。IL-1 β介导的胰岛素释放抑制和β细胞损伤与细胞内一氧化氮（NO）自由基的产生有关。因此，我们研究了NA是否阻止IL-1 β诱导的胰岛NO的产生，测量为从离体大鼠胰岛的亚硝酸盐释放，如果是这样，这种作用是否与预防IL-1 β介导的胰岛素释放抑制有关。NA剂量和时间依赖性地抑制和延迟IL-1 β诱导的胰岛NO产生。光学显微镜检测到，25 mM的NA保护免受IL-1 β诱导的胰岛损伤。5 - 50 mM NA剂量依赖性地降低了由150 pg/ml IL-1 β诱导的累积胰岛胰岛素释放的抑制。NA不能逆转IL-1 β处理的胰岛对急性葡萄糖挑战的应答能力降低。NO或亚硝酸盐不直接与NA相互作用，因为NA不减少硝普钠产生的亚硝酸盐。NO合酶抑制与L-精氨酸耗竭废除NO的生产，但只有部分减少IL-1 β诱导的抑制积累胰岛素释放。通过向L-精氨酸耗尽的培养基中加入L-精氨酸类似物不能完全抑制IL-1 β的作用，表明IL-1 β对胰岛胰岛素释放可能存在NO非依赖性作用。这些结果表明，NA介导的保护IL-1诱导的β细胞损伤的新机制，通过NA对NO的形成的抑制作用。
Nicotinamide (NA) prevents macrophage- and interleukin-1 (IL-1)-mediated beta-cell damage in vitro as well as diabetes development in animal models of insulin-dependent diabetes mellitus (IDDM). IL-1 beta-mediated inhibition of insulin release and damage to beta-cells are associated with intracellular production of nitric oxide (NO) radicals. Therefore, we studied whether NA prevented IL-1 beta-induced islet NO production, measured as nitrite release from isolated rat islets, and, if so, whether this action was associated with prevention of IL-1 beta-mediated inhibition of insulin release. NA dose- and time-dependently inhibited and delayed IL-1 beta-induced islet NO production. Light microscopy detected that 25 mM of NA protected against IL-1 beta-induced islet damage. Five to 50 mM of NA dose-dependently reduced inhibition of accumulated islet insulin release induced by 150 pg/ml of IL-1 beta. NA was not able to reverse the reduced ability of IL-1 beta-treated islets to respond to an acute glucose challenge. NO or nitrite did not interact directly with NA, because NA did not reduce sodium nitroprusside-generated nitrite. NO-synthase inhibition with L-arginine depletion abolished NO production but only partially reduced IL-1 beta-induced inhibition of accumulated insulin release. Complete inhibition of IL-1 beta effects could not be obtained by adding L-arginine analogues to L-arginine-depleted medium, indicating that an NO-independent action of IL-1 beta on islet insulin release may exist. These results suggest a novel mechanism for NA-mediated protection of IL-1-induced beta-cell damage via an inhibitory effect of NA on the formation of NO.