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

KEYWORDS:

• Acne
• FoxO1
• High glycaemic load diet
• IGF-1
• PI3K
• sebocytes
• T cells

Abbreviations

ANOVA	=	analysis of variance
APC	=	antigen-presenting cell
DAPI	=	4; 6-diamidino-2-phenylindole; dihydro-chloride
FoxO1	=	forkhead box-O1
IGF-1	=	insulin-like growth factor-1
IGF-1R	=	IGF-1 receptor
IR	=	insulin receptor
mTORC1	=	mammalian target of rapamycin complex 1
P. acnes	=	propionibacterium acnes
PFA	=	paraformaldehyde
PI3K	=	phosphoinositide-3-kinase
PPAR	=	peroxisome proliferator-activated receptor
Th	=	T helper
TLR	=	Toll-like receptor
Treg cells	=	regulatory T cells

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Additional information

Funding

This work was supported by department Dermatology & Venereology Otto-von-Guericke University Magdeburg/ Germany.