Insulin and Insulin-like growth factor-1 can activate the phosphoinositide-3-kinase /Akt/FoxO1 pathway in T cells in vitro.
Insulin and Insulin-like growth factor-1 can activate the phosphoinositide-3-kinase /Akt/FoxO1 pathway in T cells in vitro.
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DOI：
10.1080/19381980.2017.1356518
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Gollnick H
中科院分区：
文献类型：
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作者：
Mirdamadi Y;Bommhardt U;Goihl A;Guttek K;Zouboulis CC;Quist S;Gollnick H
高血糖食物增加胰岛素样生长因子1 （IGF-1）和胰岛素信号，调节内分泌反应，从而可能调节痤疮的病程。炎症和适应性免疫反应在痤疮的所有阶段都起着关键作用。最近的假说认为，高血糖食物降低核叉头盒1 （FoxO1）转录因子，最终可能诱发痤疮。本研究旨在探讨IGF-1和胰岛素对人原代T细胞PI3K /Akt/FoxO1通路的影响及体外T细胞分子功能的影响。用0.001 μM IGF-1或1 μM胰岛素+/−20 μM PI3K抑制剂LY294002刺激T细胞。T细胞也暴露于用IGF-1或胰岛素预刺激的SZ95油脂细胞上清液中。我们发现0.001µM IGF-1和1µM胰岛素激活T细胞中的PI3K通路，导致p-Akt和p-FoxO1在15和30分钟上调。细胞核fox01减少，FoxO转录活性降低。0.001µM IGF-1和1µM胰岛素可增加T细胞增殖，但对toll样受体2/4 （TLR）表达无显著影响。有趣的是，来自IGF-1或胰岛素刺激的皮脂细胞的上清液激活了T细胞中的PI3K通路，但减少了T细胞的增殖。综上所述，本研究有助于支持高血糖负荷饮食可能有助于诱导人原代T细胞PI3K通路的激活和增殖的增加。IGF-1和胰岛素刺激的皮脂细胞分泌的因子诱导T细胞的PI3K通路，减少T细胞的增殖，这可能反映了皮脂腺基底细胞的一种保护机制。
Hyper-glycemic food increases insulin-like growth factor 1 (IGF-1) and insulin signaling and regulates endocrine responses and thereby may modulate the course of acne. Inflammation and adaptive immune responses have a pivotal role in all stages of acne. Recent hypothesis suggests that hyperglycemic food reduces nuclear forkhead box-O1 (FoxO1) transcription factor and may eventually induces acne. The aim of our study was to investigate the role of IGF-1 and insulin on the phosphoinositide-3-kinase (PI3K)/Akt/FoxO1 pathway in human primary T cells and on the molecular functions of T cells in vitro. T cells were stimulated with 0.001 μM IGF-1 or 1 μM insulin +/− 20 μM PI3K inhibitor LY294002. T cells were also exposed to SZ95 sebocyte supernatants which were pre-stimulated with IGF-1 or insulin. We found that 0.001 µM IGF-1 and 1 µM insulin activate the PI3K pathway in T cells leading to up-regulation of p-Akt and p-FoxO1 at 15 and 30 minutes. Nuclear FoxO1 was decreased and FoxO transcriptional activity was reduced. 0.001 µM IGF-1 and 1 µM insulin increased T cell proliferation but have no significant effect on Toll-like receptor2/4 (TLR) expression. Interestingly, supernatants from IGF-1- or insulin-stimulated sebocytes activated the PI3K pathway in T cells but reduced T cell proliferation. Taken together, this study helps to support that high glycemic load diet may contribute to induce activation of the PI3K pathway and increase of proliferation in human primary T cells. Factors secreted by IGF-1- and insulin-stimulated sebocytes induce the PI3K pathway in T cells and reduce T cell proliferation, which probably can reflect a protective mechanism of the sebaceous gland basal cells.