Interleukin-6 Treatment Results in GLUT4 Translocation and AMPK Phosphorylation in Neuronal SH-SY5Y Cells

Abstract

Interleukin-6 (IL-6) is a pleiotropic cytokine that can be released from the brain during prolonged exercise. In peripheral tissues, exercise induced IL-6 can result in GLUT4 translocation and increased glucose uptake through AMPK activation. GLUT4 is expressed in the brain and can be recruited to axonal plasma membranes with neuronal activity through AMPK activation. The aim of this study is to examine if IL-6 treatment: (1) results in AMPK activation in neuronal cells, (2) increases the activation of proteins involved in GLUT4 translocation, and (3) increases neuronal glucose uptake. Retinoic acid was used to differentiate SH-SY5Y neuronal cells. Treatment with 100 nM of insulin increased the phosphorylation of Akt and AS160 (p < 0.05). Treatment with 20 ng/mL of IL-6 resulted in the phosphorylation of STAT3 at Tyr705 (p ≤ 0.05) as well as AS160 (p < 0.05). Fluorescent Glut4GFP imaging revealed treatment with 20ng/mL of IL-6 resulted in a significant mobilization towards the plasma membrane after 5 min until 30 min. There was no difference in GLUT4 mobilization between the insulin and IL-6 treated groups. Importantly, IL-6 treatment increased glucose uptake. Our findings demonstrate that IL-6 and insulin can phosphorylate AS160 via different signaling pathways (AMPK and PI3K/Akt, respectively) and promote GLUT4 translocation towards the neuronal plasma membrane, resulting in increased neuronal glucose uptake in SH-SY5Y cells.

Ginsenoside Rb1 Protects Against Diabetic Cardiomyopathy by Regulating the Adipocytokine Pathway

“… 30 IL-6 may influence expression of Glut4, Irs1 , and Ampk , which regulate lipid and glucose metabolism. 31 TNF-α can also downregulate the expression of PGC1α, PDK4, and CPT1, which play critical roles in regulating energy metabolism. 32 Elevated levels of circulating pro-inflammatory cytokines also indicate poor prognosis in patients with heart failure because activation of immune response in the heart leads to adverse cardiac remodeling and left ventricular dysfunction.…”

Alterations of the expression levels of glucose, inflammation, and iron metabolism related miRNAs and their target genes in the hypothalamus of STZ-induced rat diabetes model

“…The changes at protein level of HXK-2 and GCK in the hypothalamus of the STZ-treated rats predispose to enhanced glucose phosphorylation [ 55 ], while the elevated level of GLUT4 suggests that not only insulin signalling but miRNAs affected protein synthesis is also important in the expression of GLUT4 and glucose uptake. Moreover, the elevated level of inflammatory cytokines such as IL-6 can contribute to the increased GLUT4 level independently of insulin [ 56 ]. On the other hand, the raising protein level of LEPR may trigger the effect of leptin on lowering glucose concentration in the circulation [ 57 , 58 ].…”

Oligo-Fucoidan supplementation enhances the effect of Olaparib on preventing metastasis and recurrence of triple-negative breast cancer in mice

“…AMPK, a sensor of glucose limitations and cellular energy status [39,40], is activated to resolve nutrient resource-need imbalances and is critical for diabetes and cancer development. IL-6 acts on glucose metabolism [41] and AMPK activation to promote GLUT4 translocation to the neuronal plasma membrane [42], resulting in enhanced glucose uptake in neuronal cells. Relevant to the inhibition of the IL-6/p-AMPK axis by combined olaparib and Oligo-Fucoidan treatment, we found that not only glucose metabolism factors, such as glucose transporter-1 (Glut1), phosphofructokinase (PFKL), ribose 5-phosphate isomerase A (RPIA) and phosphorpyruvate kinase 2 (p-PKM2) (Tyr105) (Fig.…”