Department of Medicine and of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Metabolism. 2010 Oct;59(10):1413-20. doi: 10.1016/j.metabol.2008.11.021. Epub 2010 Feb 11.
Insulin regulation of energy metabolism is complex and involves numerous signaling cascades. Insulin has been suggested to stimulate a phospholipase that cleaves glycosylphosphatidylinositols resulting in the generation of an inositol glycan that serves as an insulin mediator. To determine if glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) may play a role in glucose metabolism, we examined the effect of overexpressing GPI-PLD using adenovirus-mediated gene transfer in C57BL/6 mice. Overexpressing GPI-PLD was associated with a decrease in fasting glucose as well as an improvement in glucose tolerance as determined by an intraperitoneal glucose tolerance test. This effect to improve glucose tolerance does not result from an increase in insulin sensitivity, as overexpressing GPI-PLD does not alter the response to insulin. In contrast, the insulin response during the glucose tolerance test in GPI-PLD-overexpressing mice was increased. Overexpressing GPI-PLD in an insulinoma cell line enhanced glucose-stimulated insulin secretion, suggesting that enhanced insulin secretion in vivo may have contributed to the improved glucose tolerance.
胰岛素对能量代谢的调节是复杂的，涉及许多信号级联。有研究表明，胰岛素可以刺激一种磷脂酶，该酶可以裂解糖基磷脂酰肌醇，从而产生一种作为胰岛素介质的肌醇糖苷。为了确定糖基磷脂酰肌醇特异性磷脂酶 D（GPI-PLD）是否在葡萄糖代谢中发挥作用，我们使用腺病毒介导的基因转移在 C57BL/6 小鼠中过表达 GPI-PLD，以研究其对葡萄糖代谢的影响。过表达 GPI-PLD 与空腹血糖降低以及通过腹腔内葡萄糖耐量试验确定的葡萄糖耐量改善有关。这种改善葡萄糖耐量的作用不是由于胰岛素敏感性增加引起的，因为过表达 GPI-PLD 不会改变对胰岛素的反应。相比之下，在过表达 GPI-PLD 的小鼠中，葡萄糖耐量试验期间的胰岛素反应增加。在胰岛素瘤细胞系中过表达 GPI-PLD 增强了葡萄糖刺激的胰岛素分泌，这表明体内增强的胰岛素分泌可能有助于改善葡萄糖耐量。
