Yang Yumei, Gong Liangliang
Department of Endocrinology and Metabolism, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang 322000, P.R. China.
Department of Rheumatology, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang 322000, P.R. China.
Exp Ther Med. 2017 Jun;13(6):2805-2811. doi: 10.3892/etm.2017.4344. Epub 2017 Apr 18.
The aim of the present study was to evaluate the effects of palmitoleate on insulin secretion and insulin mRNA levels, and to investigate the transcriptional regulation of insulin. INS-1 rat insulinoma cells were treated with palmitoleate in the presence of high glucose, and the amount of secreted insulin was measured via radioimmunoassay. Reverse transcription-quantitative polymerase chain reaction was performed to evaluate the mRNA levels of insulin and pancreatic and duodenal homeobox 1 (PDX1) under palmitoleate treatment. The levels of PDX1, peroxisome proliferator-activated receptor gamma (PPARG), extracellular signal-regulated kinase (ERK)1/2 and phosphorylated ERK1/2 were measured using western blot analysis. Low concentrations of palmitoleate significantly induced insulin secretion (P=0.024), whereas the mRNA levels of insulin and PDX1 were markedly reduced. However, the inhibitory effects were reversed with the addition of U0126, suggesting that the ERK1/2-mediated pathway may be the underlying mechanism responsible for palmitoleate-induced downregulation of insulin mRNA. Exposure of INS-1 cells to high glucose significantly increased the phosphorylation of ERK1/2 (P=0.039), which was further enhanced by palmitoleate (P=0.025). Exposure of INS-1 cells to high glucose significantly decreased PPARG (P=0.001), which was further decreased by the addition of palmitoleate. U0126 was able to reverse the palmitoleate-induced effects. In conclusion, the present study suggested that palmitoleate may induce insulin secretion and inhibit insulin mRNA expression in pancreatic β-cells.
本研究的目的是评估棕榈油酸酯对胰岛素分泌和胰岛素mRNA水平的影响，并研究胰岛素的转录调控。在高糖环境下用棕榈油酸酯处理INS-1大鼠胰岛素瘤细胞，通过放射免疫分析法测定分泌的胰岛素量。进行逆转录定量聚合酶链反应以评估棕榈油酸酯处理下胰岛素和胰腺十二指肠同源盒1（PDX1）的mRNA水平。使用蛋白质免疫印迹分析测定PDX1、过氧化物酶体增殖物激活受体γ（PPARG）、细胞外信号调节激酶（ERK）1/2和磷酸化ERK1/2的水平。低浓度的棕榈油酸酯显著诱导胰岛素分泌（P = 0.024），而胰岛素和PDX1的mRNA水平显著降低。然而，添加U0126可逆转这种抑制作用，表明ERK1/2介导的途径可能是棕榈油酸酯诱导胰岛素mRNA下调的潜在机制。将INS-1细胞暴露于高糖环境中可显著增加ERK1/2的磷酸化（P = 0.039），棕榈油酸酯可进一步增强这种作用（P = 0.025）。将INS-1细胞暴露于高糖环境中可显著降低PPARG（P = 0.001），添加棕榈油酸酯可进一步降低其水平。U0126能够逆转棕榈油酸酯诱导的作用。总之，本研究表明棕榈油酸酯可能诱导胰腺β细胞分泌胰岛素并抑制胰岛素mRNA表达。
