Insulin induces proliferation and cardiac differentiation of P19CL6 cells in a dose-dependent manner
Insulin induces proliferation and cardiac differentiation of P19CL6 cells in a dose-dependent manner
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胰岛素以剂量依赖性方式诱导P19CL6细胞增殖和心脏分化
DOI：
10.1111/dgd.12075
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发表时间：
2013-09-01
影响因子：
2.5
通讯作者：
Zang, Ming-Xi
中科院分区：
文献类型：
--
作者：
Li, Wen-Yan;Song, Yang-Liu;Zang, Ming-Xi
胰岛素是由胰腺的β细胞产生的肽激素。胰岛素在能量代谢中的作用已经得到了很好的研究，大多数注意力集中在葡萄糖的利用上，但胰岛素在细胞增殖和分化中的作用仍然不清楚。本研究首次观察到10 nmol/L胰岛素诱导P19 CL 6细胞增殖和心肌分化，而50和100 nmol/L胰岛素诱导P19 CL 6细胞凋亡并阻断P19 CL 6细胞心肌分化。实时荧光定量PCR和Western blotting分析发现，10 nmol/L胰岛素刺激可诱导细胞周期蛋白D1和α-肌球蛋白重链（α-MHC）的mRNA表达，而50/100 nmol/L胰岛素刺激则抑制其表达，BCL-2细胞死亡拮抗剂（BAD）的mRNA表达则呈相反趋势。在表达加塔-6或过氧化物酶体增殖物激活受体α（PPAR α）的P19 CL 6细胞中观察到类似的结果。我们的结果确定了胰岛素的下游靶点cyclin D1、BAD、α-MHC和加塔-4，阐明了胰岛素促进细胞增殖和分化的新的分子机制。
Insulin is a peptide hormone produced by beta cells of the pancreas. The roles of insulin in energy metabolism have been well studied, with most of the attention focused on glucose utilization, but the roles of insulin in cell proliferation and differentiation remain unclear. In this study, we observed for the first time that 10 nmol/L insulin treatment induces cell proliferation and cardiac differentiation of P19CL6 cells, whereas 50 and 100 nmol/L insulin treatment induces P19CL6 cell apoptosis and blocks cardiac differentiation of P19CL6 cells. By using real-time polymerase chain reaction (PCR) and Western blotting analysis, we found that the mRNA levels of cyclin D1 and alpha myosin heavy chain (alpha-MHC) are induced upon 10 nmol/L insulin stimulation and inhibited upon 50/100 nmol/L insulin treatment, whereas the mRNA levels of BCL-2-antagonist of cell death (BAD) exists a reverse trend. The similar results were observed in P19CL6 cells expressing GATA-6 or peroxisome proliferator-activated receptor alpha (PPAR alpha). Our results identified the downstream targets of insulin, cyclin D1, BAD, alpha-MHC, and GATA-4, elucidate a novel molecular mechanism of insulin in promoting cell proliferation and differentiation.