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Type: Artigo
Title: Interleukin-6 Increases The Expression And Activity Of Insulin-degrading Enzyme
Author: Kurauti
Mirian A.; Costa-Junior
Jose M.; Ferreira
Sandra M.; Santos
Gustavo J.; Sponton
Carlos H. G.; Carneiro
Everardo M.; Telles
Guilherme D.; Chacon-Mikahil
Mara P. T.; Cavaglieri
Claudia 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.
Subject: Dependent Diabetes-mellitus
Activated Protein-kinase
Human Skeletal-muscle
Cafeteria Diet
Rat Islets
Editor: Nature Publishing Group
Citation: Scientific Reports. Nature Publishing Group, v. 7, p. , 2017.
Rights: aberto
Identifier DOI: 10.1038/srep46750
Date Issue: 2017
Appears in Collections:Unicamp - Artigos e Outros Documentos

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