Sun Qin, Li Ling, Li Renzhe, Yang Mengliu, Liu Hua, Nowicki Michael J, Zong Haihong, Xu Jun, Yang Gangyi
Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Ann Med. 2009;41(4):311-20. doi: 10.1080/07853890902729760.
Visfatin/PBEF/Nampt is an adipose-derived hormone proposed to exert insulin-mimicking effects and play a positive role in attenuating insulin resistance. However, the precise mechanisms underlying the beneficial effects of visfatin/PBEF/Nampt on insulin sensitivity remain unknown.
Euglycemic-hyperinsulinemic clamps were used in the same groups of rats to study the in vivo effect of visfatin/PBEF/Nampt on insulin sensitivity and glucose/lipid metabolism before and after the overexpression of visfatin/PBEF/Nampt protein, which was carried out by injection of pcDNA3.1-visfatin plasmid.
On day 4 after plasmid injection, plasma visfatin/PBEF/Nampt protein levels were significantly increased and displayed a hypocholesterolemic effect in both normal-chow (NC) and high-fat diet (HT) animals with pcDNA3.1-visfatin treatment. A second glucose clamp also demonstrated increased insulin sensitivity in pcDNA3.1-visfatin animals. Consistent with the clamp data, the extent of insulin receptor substrate (IRS)-1 tyrosine phosphorylation in response to insulin was significantly enhanced in the liver and adipose tissues. In addition, the mRNA expression of peroxisome proliferator-activated receptor-gamma (PPARgamma) and sterol regulatory element-binding proteins 2 (SREBP-2) in the liver and adipose tissues was also significantly upregulated in these animals.
These results demonstrate that visfatin/PBEF/Nampt improves insulin sensitivity and exerts its hypocholesterolemic effects at least partially through upregulation of the tyrosine phosphorylation of IRS-1 protein and the mRNA levels of PPARgamma and SREBP-2.
内脂素/前B细胞克隆增强因子/烟酰胺磷酸核糖转移酶（Visfatin/PBEF/Nampt）是一种脂肪源性激素，被认为具有胰岛素模拟作用，并在减轻胰岛素抵抗方面发挥积极作用。然而，内脂素/前B细胞克隆增强因子/烟酰胺磷酸核糖转移酶对胰岛素敏感性产生有益作用的具体机制仍不清楚。
在同一组大鼠中使用正常血糖-高胰岛素钳夹技术，以研究通过注射pcDNA3.1-内脂素质粒使内脂素/前B细胞克隆增强因子/烟酰胺磷酸核糖转移酶蛋白过表达前后，其对胰岛素敏感性以及葡萄糖/脂质代谢的体内作用。
质粒注射后第4天，pcDNA3.1-内脂素处理的正常饮食（NC）和高脂饮食（HT）动物的血浆内脂素/前B细胞克隆增强因子/烟酰胺磷酸核糖转移酶蛋白水平显著升高，并呈现出降胆固醇作用。第二次葡萄糖钳夹实验也表明，pcDNA3.1-内脂素处理的动物胰岛素敏感性增加。与钳夹实验数据一致，肝脏和脂肪组织中胰岛素受体底物（IRS）-1酪氨酸磷酸化对胰岛素的反应程度显著增强。此外，这些动物肝脏和脂肪组织中过氧化物酶体增殖物激活受体γ（PPARγ）和固醇调节元件结合蛋白2（SREBP-2）的mRNA表达也显著上调。
这些结果表明，内脂素/前B细胞克隆增强因子/烟酰胺磷酸核糖转移酶可改善胰岛素敏感性，并至少部分通过上调IRS-1蛋白的酪氨酸磷酸化以及PPARγ和SREBP-2的mRNA水平发挥其降胆固醇作用。
