Insulin and Insulin-like growth factor-1 can activate the phosphoinositide-3-kinase /Akt/FoxO1 pathway in T cells<i>in vitro</i>

Abstract

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 mM IGF-1 or 1 mM insulin C/ 20 mM 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 mM IGF-1 and 1 mM 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 mM IGF-1 and 1 mM 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.