Skop V, Kontrová K, Zídek V, Pravenec M, Kazdová L, Mikulík K, Sajdok J, Zídková J
Institute of Chemical Technology, Department of Biochemistry and Microbiology, Prague, Czech Republic.
Physiol Res. 2010;59(4):615-618. doi: 10.33549/physiolres.931845. Epub 2009 Nov 20.
Visfatin was originally described as an adipokine with insulin mimetic effects. Recently, it was found that visfatin is identical with the Nampt (nicotinamide phosphoribosyltransferase) gene that codes for an intra- and extracellular NAD biosynthetic enzyme and is predominantly expressed outside the adipose tissue. In the current study, we found strong protein and mRNA expression of visfatin in rat heart, liver, kidney, and muscle, while the expression of visfatin in visceral fat was significantly lower and undetectable in subcutaneous fat. The insulin-mimetic effects of visfatin (extracellular form of Nampt or eNampt) are controversial and even less is known about autocrine effects of visfatin (intracellular form of Nampt or iNampt). Since liver plays a major role in glucose metabolism, we studied visfatin effects on insulin-stimulated cellular glucose uptake in Fao rat hepatocytes using RNA interference (RNAi). RNAi-mediated downregulation of visfatin expression in Fao cells was associated with significantly reduced NAD biosynthesis (0.3+/-0.01 vs. 0.5+/-0.01 mmol/h/g, P<0.05) and with significantly decreased incremental glucose uptake after stimulation with insulin when compared to controls with normal expression of visfatin (0.6+/-0.2 vs. 2.2+/-0.5 nnmol/g/2 h, P=0.02). These results provide evidence that visfatin exhibits important autocrine effects on sensitivity of liver cells to insulin action possibly through its effects on NAD biosynthesis.
内脂素最初被描述为一种具有胰岛素模拟作用的脂肪因子。最近，发现内脂素与烟酰胺磷酸核糖转移酶（Nampt）基因相同，该基因编码一种细胞内和细胞外的NAD生物合成酶，且主要在脂肪组织外表达。在本研究中，我们发现大鼠心脏、肝脏、肾脏和肌肉中有很强的内脂素蛋白和mRNA表达，而在内脏脂肪中内脂素的表达明显较低，在皮下脂肪中则检测不到。内脂素（Nampt的细胞外形式或eNampt）的胰岛素模拟作用存在争议，而关于内脂素（Nampt的细胞内形式或iNampt）的自分泌作用了解更少。由于肝脏在葡萄糖代谢中起主要作用，我们使用RNA干扰（RNAi）研究了内脂素对Fao大鼠肝细胞中胰岛素刺激的细胞葡萄糖摄取的影响。与内脂素正常表达的对照组相比，RNAi介导的Fao细胞内脂素表达下调与NAD生物合成显著减少（0.3±0.01 vs. 0.5±0.01 mmol/h/g，P<0.05）以及胰岛素刺激后葡萄糖摄取增量显著降低有关（0.6±0.2 vs. 2.2±0.5 nnmol/g/2 h，P=0.02）。这些结果提供了证据，表明内脂素可能通过其对NAD生物合成的影响，对肝细胞对胰岛素作用的敏感性表现出重要的自分泌作用。
