Role of nitric oxide in obesity-induced beta cell disease
Role of nitric oxide in obesity-induced beta cell disease
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DOI：
10.1172/jci119534
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发表时间：
1997-07-15
影响因子：
15.9
通讯作者：
Unger, RH
中科院分区：
文献类型：
--
作者：
Shimabukuro, M;Ohneda, M;Unger, RH
在这里，我们报告，游离脂肪酸诱导的抑制胰岛素输出在糖尿病前期Zucker糖尿病脂肪（ZDF）大鼠介导的NO。当正常胰岛细胞培养在2 mM FFA，NO的生产和基础胰岛素分泌略有增加。在培养的糖尿病前期ZDF胰岛中，FFA诱导NO升高4倍，诱导型一氧化氮合酶（iNOS）mRNA表达上调，胰岛素分泌减少;降低NO的烟酰胺和氨基胍都阻止FFA介导的iNOS mRNA增加，降低NO，并使胰岛素分泌的损失最小化，在体内烟酰胺或氨基胍治疗糖尿病前期ZDF大鼠阻止了胰岛中iNOS的表达，降低了β细胞功能障碍，同时阻断了β细胞破坏和高血糖症。我们的结论是NO降低剂预防肥胖大鼠的脂肪形成性糖尿病。
Here we report that free fatty acid-induced suppression of insulin output in prediabetic Zucker diabetic fatty (ZDF) rats is mediated by NO. When normal islets were cultured in 2 mM FFA, NO production and basal insulin secretion increased slightly. In cultured prediabetic ZDF islets, FFA induced a fourfold greater rise in NO, upregulated mRNA of inducible nitric oxide synthase (iNOS), and reduced insulin output; both nicotinamide and aminoguanidine, which lower NO, prevented the FFA-mediated increase in iNOS mRNA, reduced NO, and minimized the loss of insulin secretion, In vivo nicotinamide or aminoguanidine treatment of prediabetic ZDF rats prevented the iNOS expression in islets and decreased beta cell dysfunction while blocking beta cell destruction and hyperglycemia. We conclude that NO-lowering agents prevent adipogenic diabetes in obese rats.