·糖尿病基础研究·

　　【摘要】 目的 探讨脑室内高水平Nesfatin-1(1-82)重组蛋白对大鼠糖脂代谢及其相关酶的影响。 方法 构建大鼠第三脑室微量输注系统，根据输注的不同将大鼠分为Nesfatin-1蛋白输注组(A组)和人工脑脊液输注组(B组)，采用扩展胰岛素钳夹术评定Nesfatin-1蛋白对肝糖脂代谢的影响，采用Real-Time PCR和酶动力学方法测定葡萄糖-6-磷酸酶(G-6-P)和磷酸烯醇式丙酮酸羧激酶((PEPCK )mRNA)表达和活性变化。 结果 在钳夹稳定状态下，A组葡萄糖输注率(GIR)高于B组[，((28.3±1.4) mg/(kg·min) vs. (23.0±1.8)mg/(kg·min)，P<0.01]。A组葡萄糖清除率(GRd)葡萄糖清除率(GRd)高于B组[((34.9±1.3) mg/(kg·min) vs (31.8±1.8)mg/(kg·min)，P<0.01])。RT-PCR结果显示，A组PEPCK mRNA表达与PEPCK酶活性均低于B组。 结论 中枢Nesfatin -1(1-82)短期灌注增加了大鼠机体胰岛素敏感性，并抑制了肝糖异生。

　　【关键词】Nesfatin-1;第三脑室;微量输注系统输注泵;糖脂脂类代谢;胰岛素钳夹葡萄糖钳夹技术;大鼠

The effect of intracerebroventricular infusion of recombinant protein Nesfatin-1 (1-82) on glucose and lipid metabolism YE Fei, ZHU Wei, YANG Gang-yi, et al. Department of Endocrinology, the Second Affiliated Hospital, Chongqing University of Medical Science, ChE Fei, ZHU Wei, YANG Gang-yi, et al. Department of Endocrinology, The Second Affiliated Hospital, Chongqing University of Medical Science, Chongqing 400010,Chinaongqing 400010,China

Corresponding author: YANG Gang-yi, E-mail: gangyiyang@yahoo.com.cn

　　【Abstract】 Objective To investigate the effects of high lever of Nesfatin-1 (1-82) in ventricle on glucose and lipid metabolism and the related enzymes in rats. Methods the The micro infusion system of the third ventricle was constructed. Rats were divided into two groups. One group was given nesfatin-1 (1-82) infusion ( A group, n=10), and another group was given artificial cerebrospinal fluid infusion (B group, n=10) in the third ventricle. The insulin sensitivity and glucose and lipid metabolism were assessed by the hyperinsulinemic- euglycemic clamp technique using 3-[3H] glucose as a tracer. The mRNA expressions of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6- phosphatase (G-6-P) were assessed by RT-PCR, and their activity were determined by UV spectrophotometer. Results During the steady-state of clamp, Glucose infusion rate(GIR) in NN group were significantly higher than in NC group[ (28.3±1.4 )vs(23.0±1.7) mg/(kg·min)，P<0.01]. In the end of clamp, glucose disappearance rate (GRd) was significantly higher in NN group than that in NC group[ (34.9± 1.3) vs (31.8±1.8)，P<0.01]. The RT-PCR showed the PEPCK mRNA expression of liver tissues in NN group was significantly lower compared with NC group[(10.67±0.95) vs. (21.04±0.34)，P<0.01], and the PEPCK activity in NN group was also lower than NC group[ (10.7±0.9) vs. (21.0±0.3) mU/mg， P<0.01]. Conclusion Intracerebroventricular infusion of Nesfatin-1 (1-82) in a small doses can enhance insulin sensitivity, and suppress gluconeogenesis.

　　【Key words】Nesfatin-1; Third,Ventricle ventricle; ; micro iInfusion systempumps; Glucose and lLipid metabolism; Hyperinsulinemic-euglycemicGlucose clamp clamp, technique;Rates