Experimental NIDDM - Development of a new model in adult rats administered streptozotocin and nicotinamide
Experimental NIDDM - Development of a new model in adult rats administered streptozotocin and nicotinamide
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DOI：
10.2337/diabetes.47.2.224
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发表时间：
1998-02-01
期刊：
影响因子：
7.7
通讯作者：
Ribes, G
中科院分区：
文献类型：
--
作者：
Masiello, P;Broca, C;Ribes, G
我们利用适当剂量的烟酰胺对链脲佐菌素（STZ）的β-细胞毒性作用的部分保护作用，在成年大鼠中建立了一种新的实验性糖尿病综合征，该综合征在胰岛素对葡萄糖和磺脲类药物的反应性方面似乎比其他可用的动物模型更接近NIDDM，在3月龄Wistar大鼠中测试的各种剂量的烟酰胺（100-350 mg/kg体重）中，在STZ给药（65 mg/kg i. v.）产生了最多的中度和稳定的非空腹高血糖动物（155 +/- 3 vs，对照组121 +/- 3 mg/dl; P < 0.05）和40%的胰腺胰岛素抵抗保留。我们还评估了诱导糖尿病后4-9周的体外和体内β细胞功能。在离体灌注胰腺中，胰岛素对葡萄糖升高的反应（5-11 mmol/l）明显存在，尽管相对于对照组显著降低胰岛素对甲苯磺丁脲的敏感性显著高于对照组（P < 0.01），对甲苯磺丁脲的敏感性显著高于对照组（P < 0.01），对甲苯磺丁脲的敏感性显著高于对照组（P < 0.01）。19 mol/l的精氨酸浓度与正常胰腺相似。糖尿病动物灌流胰腺对精氨酸也表现出明显的超敏反应（7 mmol/l），在大鼠中，给予STZ钉烟酰胺，静脉内葡萄糖耐量试验显示葡萄糖耐量和胰岛素反应性明显异常，有趣的是，甲苯磺丁脲给药（40 mg/kg i. v.）可逆转这些异常。总之，这种新的NIDDM综合征与胰腺胰岛素储备减少，这是类似于人类NIDDM，因为它有一个。对葡萄糖的显著响应（尽管动力学异常）和对甲苯磺丁脲的保留的敏感性可以为新促胰岛素剂的药理学研究提供特别有利的工具。
We took advantage of the partial protect on exerted by suitable dosages of nicotinamide against the beta-cytotoxic effect of streptozotocin (STZ) to create a new experimental diabetic syndrome in adult rats that appears closer to NIDDM than other available animal models with regard to insulin responsiveness to glucose and sulfonylureas, Among the various dosages of nicotinamide tested in 3-month-old Wistar rats (100-350 mg/kg body wt), the dosage of 230 mg/kg, given intraperitoneally 15 min before STZ administration (65 mg/kg i.v.) yielded a maximum of animals with moderate and stable nonfasting hyperglycemia (155 +/- 3 vs, 121 +/- 3 mg/dl in controls; P < 0.05) and 40% preservation of pancreatic insulin stors. We also evaluated beta-cell function both in vitro and in vivo 4-9 weeks after inducing diabetes. In the isolated perfused pancreas, insulin response to glucose elevation (5-11 mmol/l) was clearly present, although significantly reduced with respect to controls (P < 0.01), Moreover, the insulin response to tolbutamide (0.19 mol/l) was similar to that observed in normal pancreases, Perfused pancreases from diabetic animals also exhibited a striking hypersensitivity to arginine infusion (7 mmol/l), In rats;administered STZ pins nicotinamide, intravenous glucose tolerance tests revealed clear abnormalities in glucosc tolerance and insulin responsiveness, which were interestingly reversed by tolbutamide administration (40 mg/kg i.v.). In conclusion, this novel NIDDM syndrome with reduced pancreatic insulin stores, which is similar to human NIDDM in that it has a. significant response to glucose (although abnormal in kinetics) and preserved sensitivity to tolbutamide, may provide a particularly advantageous tool fur pharmacological investigations of new insulinotropic agents.