School of Life and Health Sciences, Aston Research Centre for Healthy Ageing, Aston University, Birmingham B4 7ET, UK.
J Mol Endocrinol. 2010 Mar;44(3):171-8. doi: 10.1677/JME-09-0071. Epub 2009 Nov 11.
The role of the adipocyte-derived factor visfatin in metabolism remains controversial, although some pancreatic beta-cell-specific effects have been reported. This study investigated the effects of visfatin upon insulin secretion, insulin receptor activation and mRNA expression of key diabetes-related genes in clonal mouse pancreatic beta-cells. beta-TC6 cells were cultured in RPMI 1640 and were subsequently treated with recombinant visfatin. One-hour static insulin secretion was measured by ELISA. Phospho-specific ELISA and western blotting were used to detect insulin receptor activation. Real-time SYBR Green PCR array technology was used to measure the expression of 84 diabetes-related genes in both treatment and control cells. Incubation with visfatin caused significant changes in the mRNA expression of several key diabetes-related genes, including marked up-regulation of insulin (9-fold increase), hepatocyte nuclear factor (HNF)1beta (32-fold increase), HNF4alpha (16-fold increase) and nuclear factor kappaB (40-fold increase). Significant down-regulation was seen in angiotensin-converting enzyme (-3.73-fold) and UCP2 (-1.3-fold). Visfatin also caused a significant 46% increase in insulin secretion compared to control (P<0.003) at low glucose, and this increase was blocked by co-incubation with the specific nicotinamide phosphoribosyltransferase inhibitor FK866. Both visfatin and nicotinamide mononucleotide induced activation of both insulin receptor and extracellular signal-regulated kinase (ERK)1/2, with visfatin-induced insulin receptor/ERK1/2 activation being inhibited by FK866. We conclude that visfatin can significantly regulate insulin secretion, insulin receptor phosphorylation and intracellular signalling and the expression of a number of beta-cell function-associated genes in mouse beta-cells.
脂联素在代谢中的作用仍然存在争议，尽管已经报道了一些胰岛β细胞特异性作用。本研究探讨了脂联素对克隆鼠胰岛β细胞胰岛素分泌、胰岛素受体激活和关键糖尿病相关基因 mRNA 表达的影响。β-TC6 细胞在 RPMI 1640 中培养，然后用重组脂联素处理。通过 ELISA 测量 1 小时的静态胰岛素分泌。磷酸特异性 ELISA 和 Western blot 用于检测胰岛素受体激活。实时 SYBR Green PCR 阵列技术用于测量处理和对照细胞中 84 个与糖尿病相关的基因的表达。脂联素孵育导致几个关键的糖尿病相关基因的 mRNA 表达发生显著变化，包括胰岛素（增加 9 倍）、肝细胞核因子（HNF）1β（增加 32 倍）、HNF4α（增加 16 倍）和核因子κB（增加 40 倍）的显著上调。血管紧张素转换酶（减少 3.73 倍）和 UCP2（减少 1.3 倍）的表达明显下调。与对照相比，脂联素在低糖条件下还导致胰岛素分泌显著增加 46%（P<0.003），而这种增加被特异性烟酰胺磷酸核糖基转移酶抑制剂 FK866 阻断。脂联素和烟酰胺单核苷酸都能诱导胰岛素受体和细胞外信号调节激酶（ERK）1/2 的激活，而 FK866 抑制了脂联素诱导的胰岛素受体/ERK1/2 激活。我们得出结论，脂联素可以显著调节小鼠β细胞胰岛素分泌、胰岛素受体磷酸化和细胞内信号转导以及一些β细胞功能相关基因的表达。
