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Characterization of STZ-lnduced Type 2 Diabetes in Zucker Fatty Rats

机译:STZ诱导Zucker肥胖大鼠的2型糖尿病的特征

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The Zucker fatty (ZF) rat is a disease model of obesity and metabolic syndrome, such as hyperlipidemia and insulin resistance, resulting from hyperphagia owing to the loss of function of the leptin receptor, but it rarely develops hyperglycemia. We examined the effects of different doses of streptozotocin (STZ). A low dosage of STZ (30 mg/kg body weight, i.p.) elevated blood glucose levels in ZF rats up to 300 mg/dl within a week, and to nearly 500 mg/dl by 5 weeks after injection of STZ. Besides hyperglycemia, STZ-treated ZF (STZ-ZF) rats retained metabolic syndrome features such as hyperlipidemia and hyperinsulinemia. The stimulated insulin secretion in response to orally-loaded glucose disappeared completely in STZ-ZF rats. Although there were no significant differences in the morphology of pancreatic islets between vehicle-treated ZF (Cont-ZF) and STZ-ZF rats, the insulin content was markedly decreased in STZ-ZF rats. The hepatic gene expression for gluconeogenic enzymes was upregulated in STZ-ZF rats compared with Cont-ZF rats. Metformin lowered the blood glucose levels of STZ-ZF rats in a dose-dependent manner. These results suggest that STZ-ZF rats are useful for studies of T2DM and for the evaluation of the efficacy of anti-diabetic drugs.
机译:Zucker脂肪(ZF)大鼠是肥胖症和代谢综合征的疾病模型,例如高脂血症和胰岛素抵抗,是由于瘦素受体功能丧失引起的食欲过高而引起的,但很少发生高血糖症。我们检查了不同剂量的链脲佐菌素(STZ)的影响。低剂量的STZ(30 mg / kg体重,腹膜内)可使ZF大鼠的血糖水平在一周内升高至300 mg / dl,到注射STZ后5周达到近500 mg / dl。除高血糖症外,经STZ治疗的ZF(STZ-ZF)大鼠还保留了代谢综合征的特征,例如高脂血症和高胰岛素血症。 STZ-ZF大鼠响应口服葡萄糖刺激的胰岛素分泌完全消失。尽管在用媒介物治疗的ZF(Cont-ZF)和STZ-ZF大鼠之间,胰岛的形态没有显着差异,但在STZ-ZF大鼠中,胰岛素含量明显降低。与Cont-ZF大鼠相比,STZ-ZF大鼠的糖原异生酶肝基因表达上调。二甲双胍以剂量依赖的方式降低了STZ-ZF大鼠的血糖水平。这些结果表明STZ-ZF大鼠可用于研究T2DM和评估抗糖尿病药的功效。

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