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.
Highlights
The human brain represents only 2–3% of total body mass, it accounts for ~20–30%of the whole-body energy expenditure
The purpose of this study was three pronged: the first objective was to determine if acute IL-6 exposure could activate AMPK in SH-SY5Y neuronal cells, the second objective was to determine if proteins involved in GLUT4 translocation were activated with acute IL-6 exposure, with the overall goal of investigating whether IL-6 can promote GLUT4 translocation, and the third objective was to determine if IL-6 exposure increased cellular glucose uptake
Post treatment there was an increase in Akt phosphorylation at the Serine 473 site with 100nM insulin compared to the control group (Figure 1A, p < 0.001)
Summary
This energy is mostly derived from glucose, of which the brain utilizes ~100–150 g per day [1,2]. The use of positron emission tomography (PET) to analyze cerebral glucose utilization has become one of the most reliable tools for diagnosing and assessing the progression of AD [7]. AD demonstrated that metabolic reductions precede the onset of clinical symptoms by several years and correlate with the diagnosis and severity of AD [8]. Given this information, the deregulation of glucose uptake and utilization in AD has become an important therapeutic target
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