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

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 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.

PI3K/AKT Signal Pathway: A Target of Natural Products in the Prevention and Treatment of Alzheimer’s Disease and Parkinson’s Disease

“…After phosphorylated by the upstream signal, PI3K/AKT executes diverse biological actions by phosphorylating or forming complexes for a range of downstream molecules, such as the FoxO family members, GSK-3β, mTOR, and actin-related protein, among others ( Mirdamadi et al, 2017 ; Matsuo et al, 2018 ). The activation of this signaling pathway and its downstream regulation are basically illustrated in Supplementary Figures S1 or S2 .…”

Effect of oral isotretinoin on the nucleo‐cytoplasmic distribution of FoxO1 and FoxO3 proteins in sebaceous glands of patients with acne vulgaris

“…There is increasing interest in the role of FoxO1 and FoxO3 in cutaneous homeostasis and skin diseases . In 2010, inactivation of nuclear FoxO1, a key downstream regulator of the insulin‐like growth factor‐1 (IGF‐1)/AKT pathway, has been deduced to play a key role in the pathogenesis of acne vulgaris, which has been disputed and finally confirmed in immortalized SZ95 sebocytes, sebaceous gland‐rich skin biopsies of acne patients and insulin‐ and IGF‐1 stimulated T cells . Central to FoxO1 and FoxO3 regulation is a shuttling system, which confines FoxOs to either the nucleus or the cytoplasm .…”

FoxO1 enhances differentiation and apoptosis in human primary keratinocytes

“…High (0.1 and 1 μmol/L) but not physiologic concentrations (1 and 10 nmol/L) of IGF‐1 stimulated lipogenesis through PI3K/Akt/FoxO1 pathway in SZ95 sebocytes . 1 nmol/L IGF‐1 promoted proliferation via PI3K/Akt/FoxO1 pathway in human primary T cells . Collectively, our results suggest that subphysiological doses (0.1‐2 nmol/L) of IGF‐1 may reduce keratinocyte differentiation through PI3K/Akt/FoxO1 pathway.…”