下丘脑Nesfatin-1/NUCB2对糖尿病小鼠摄食的影响

目的:探讨下丘脑神经肽NUCB2与Tsumura Suzuki(TS)多基因突变2型糖尿病(T2DM)小鼠摄食过多的关系。方法:将动物分为Tsumura Suzuki糖尿病(TSD)小鼠、正常小鼠;监视器监测小鼠摄食量;分析血生化指标;定量RT-PCR分析摄食相关神经肽m RNA表达水平;放射免疫分析法检测nesfatin-1蛋白水平。结果:与年龄匹配的TSN小鼠相比,TSD小鼠在1月龄就存在体重增加(P<0.05)和高瘦素血症(P<0.05),3-12月龄出现贪食(P<0.05)、高血糖(P<0.05)、高血脂(P<0.05)和高胰岛素血症(P<0.05),且3-12月龄时厌食肽nesfatin-1前体核连蛋白2(NUCB2)m RNA和nesfatin-1蛋白水平均显著降低(P<0.05~0.01);TSD小鼠下丘脑甘丙肽、黑色素浓集素、神经肽Y及前黑素细胞皮质素原m RNA水平也有显著改变(P<0.05)。结论:下丘脑NUCB2介导信号通路破坏可能导致TSD小鼠摄食过多。

The Effects of Hypothalamic Nesfatin-1/NUCB2 on Feeding in Diabetes Mice

Objective:To discuss the relationship between hypothalamic neuropeptide NUCB2 and hyperphagic feeding in Tsumura Suzuki Diabetes (TSD) mice, a model of type 2 diabetes with polygenic abnormalities.Methods:Animals can be divided into Male Tsumura Suzuki Diabetes (TSD) mice, Tsumura Suzuki normal (TSN) mice. Food intake in mice was monitored and blood chemistry was analyzed. Quantitative real-time polymerase chain reaction (PCR) assay was used to measure the expression level of feeding-related neuropeptide mRNA; radiation immunoassay was used to detect the protein level of nesfatin-1.Results:TSD mice showed an increase in body weight (P<0.05) and hyperleptinemia (P<0.05) from 1 month of age and hyperphagic feeding (P<0.05), hyperglycemia (P<0.05), hyperlipidemia (P<0.05) and hyperinsulinemia (P<0.05) from 3 to 12 months of age compared with age-matched non-diabetic control TSN mice. The mRNA and protein levels of nucleobindin-2 (NUCB2), the precursor of the anorexigenic neuropeptide nesfatin-1, was significantly decreased (P<0.05~0.01) in the hypothalamus of TSD mice compared with that in TSN mice from 3 to 12 months of age. The mRNA levels of galanin, melanin-concentrating hormone, neuropeptide Y, and pro-opiomelanocortin were significantly changed (P<0.05) in the hypothalamus in TSD mice at several time points.Conclusion:The results suggest that the disrupted control of hypothalamic NUCB2-mediated signaling may contribute to hyperphagic feeding in TSD mice.