Insulin induces neurite outgrowth via SIRT1 in SH-SY5Y cells

Insulin plays diverse roles, including learning and memory, in the central nervous system. SIRT1 has been reported to be involved in the processes of normal learning, memory, and synaptic plasticity. However, whether insulin is directly involved in regulating SIRT1 expression in neurons or whether it affects synapses remains largely unknown. Here, we show that insulin promotes neurite outgrowth and increases SIRT1 expression in SH-SY5Y cells. LY294002, a phosphatidylinositol 3-kinase inhibitor, inhibited the expression of insulin-induced increases in SIRT1. Conversely, the downregulation of SIRT1 using a SIRT1 inhibitor and SIRT1-siRNA resulted in a significant reduction in the length of neurite outgrowth. Taken together, these results suggest that the regulation of SIRT1 by insulin is important for the neurite outgrowth of neuroblastoma cells.

Insulin induces neurite outgrowth via SIRT1 in SH-SY5Y cells. (A) SH-SY5Y cells were treated with 100 nM insulin for 12 h and then subjected to Western blotting with anti-SIRT1. The SIRT1 protein levels increased in the insulin-treated cells. (B) The cells were growth-arrested with serum-free medium for 12 h and then cultured with 100 nM insulin, 20 μM LY294002 or 100 nM insulin + 20 μM LY294002 for 36 h. PI3-kinase inhibitor inhibits the insulin-induced expression of SIRT1 protein. (C) SIRT1-siRNAs or control siRNAs were transfected into SH-SY5Y cells 36 h. SIRT1-siRNA represses insulin-induced neurite outgrowth. Bars = 50 μM. At least 100 cells were assessed in each experiment. ∗p < 0.05; #p < 0.01 vs. control.59Highlights► Insulin increases SIRT1 expression in SH-SY5Y cells. ► LY294002 inhibited the expression of insulin-induced increases in SIRT1. ► Insulin affects the length of neurite outgrowth via SIRT1 in SH-SY5Y cells. ► Insulin exerts its impact on the nervous system through SIRT1 mediation.