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- Title
Interleukin-6 increases the expression and activity of insulin-degrading enzyme.
- Authors
Kurauti, Mirian A.; Costa-Júnior, José M.; Ferreira, Sandra M.; Santos, Gustavo J.; Sponton, Carlos H. G.; Carneiro, Everardo M.; Telles, Guilherme D.; Chacon-Mikahil, Mara P. T.; Cavaglieri, Cláudia R.; Rezende, Luiz F.; Boschero, Antonio C.
- 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.
- Publication
Scientific Reports, 2017, p46750
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/srep46750