The Lipid Research Laboratory, Technion Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences, Rambam Medical Center, Haifa 31096, Israel.
Atherosclerosis. 2011 Dec;219(2):510-8. doi: 10.1016/j.atherosclerosis.2011.07.119. Epub 2011 Aug 4.
To analyze the direct effects of paraoxonase-1 (PON1) on diabetes development and on β-cell insulin release.
Injection of rePON1 to mice, prior to STZ-induced diabetes, resulted in reduced incidence of diabetes, as well as, in higher serum insulin levels. Incubation of β-cells with PON1 also dose-dependently increased insulin secretion and its cellular content. PON1 increased cell survival under high glucose levels, but not under high STZ concentrations. The addition of the PON1 carrier in the circulation - HDL, to βTC3 cell line, had an additive effect on PON1-induced insulin secretion. PON1 administration to mice or incubation with β-cells was associated with a substantial decreased oxidative stress. Just like PON1, the dietary anti-oxidants, pomegranate juice, punicalagin (major polyphenol in pomegranate) or vitamin E, also increased insulin release from βTC3, but unlike PON1, failed to increase insulin cellular content, suggesting a possible role for PON1 in insulin biosynthesis, separately from PON1 antioxidative effect. Both, PON1 catalytic activity and PON1 association to HDL, were not required for PON1 stimulation of insulin release from β-cells. However, the PON1 free sulfhydryl group was shown to be essential for insulin release by PON1, as blocking the PON1 SH group, abolished PON1 stimulatory effect on insulin secretion.
PON1 is a potent anti-diabetic enzyme that exerts this protection against diabetes through its antioxidative, as well as via its insulin stimulation properties on β-cells.
分析对氧磷酶-1（PON1）对糖尿病发展和β细胞胰岛素分泌的直接影响。
在 STZ 诱导糖尿病之前，向小鼠注射重组 PON1 可降低糖尿病的发生率，并提高血清胰岛素水平。PON1 孵育β细胞也可剂量依赖性地增加胰岛素分泌及其细胞含量。PON1 可增加高葡萄糖水平下的细胞存活率，但对高 STZ 浓度下的细胞存活率无影响。将 PON1 载体（HDL）添加到βTC3 细胞系的循环中，可增强 PON1 诱导的胰岛素分泌的作用。PON1 给药或孵育β细胞与显著降低氧化应激有关。与 PON1 一样，膳食抗氧化剂，石榴汁、安石榴甙（石榴中的主要多酚）或维生素 E，也可增加βTC3 细胞的胰岛素分泌，但与 PON1 不同的是，它们不能增加胰岛素的细胞含量，这表明 PON1 可能在胰岛素生物合成中具有不同于 PON1 抗氧化作用的作用。PON1 对β细胞胰岛素释放的刺激作用既不需要 PON1 的催化活性，也不需要 PON1 与 HDL 的结合。然而，PON1 的游离巯基基团对于 PON1 诱导的胰岛素释放是必需的，因为阻断 PON1 的 SH 基团会使 PON1 对胰岛素分泌的刺激作用丧失。
PON1 是一种有效的抗糖尿病酶，它通过抗氧化作用以及对β细胞的胰岛素刺激作用来发挥这种保护作用，从而预防糖尿病的发生。
