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Interleukin-6 increases the expression and activity of insulin-degrading enzyme

2017; Nature Portfolio; Volume: 7; Issue: 1 Linguagem: Inglês

10.1038/srep46750

2045-2322

Mirian Ayumi Kurauti, José Maria Costa-Júnior, Sandra Mara Ferreira, Gustavo Jorge dos Santos, Carlos H. Sponton, Everardo M. Carneiro, Guilherme Defante Telles, Mara Patrícia Traina Chacon‐Mikahil, Cláudia Regina Cavaglieri, Luiz Fernando de Rezende, Antônio C. Boschero,

Exercise and Physiological Responses

Abstract Impairment of the insulin-degrading enzyme (IDE) is associated with obesity and type 2 diabetes mellitus (T2DM). Here, we used 4-mo-old male C57BL/6 interleukin-6 (IL-6) knockout mice (KO) to investigate the role of this cytokine on IDE expression and activity. IL-6 KO mice displayed lower insulin clearance in the liver and skeletal muscle, compared with wild type (WT), due to reduced IDE expression and activity. We also observed that after 3-h incubation, IL-6, 50 and 100 ng ml −1 , increased the expression of IDE in HEPG2 and C2C12 cells, respectively. In addition, during acute exercise, the inhibition of IL-6 prevented an increase in insulin clearance and IDE expression and activity, mainly in the skeletal muscle. Finally, IL-6 and IDE concentrations were significantly increased in plasma from humans, after an acute exercise, compared to pre-exercise values. Although the increase in plasma IDE activity was only marginal, a positive correlation between IL-6 and IDE activity, and between IL-6 and IDE protein expression, was observed. Our outcomes indicate a novel function of IL-6 on the insulin metabolism expanding the possibilities for new potential therapeutic strategies, focused on insulin degradation, for the treatment and/or prevention of diseases related to hyperinsulinemia, such as obesity and T2DM.