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

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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.

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 7, APR 21 2017.
• Citações Web of Science: 9

Resumo

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. (AU)

• Processo FAPESP: 15/12611-0 - Mecanismos moleculares envolvidos na disfunção e morte de células beta pancreáticas no Diabetes mellitus: estratégias para a inibição desses processos e para a recuperação da massa insular
• Beneficiário: Antonio Carlos Boschiero
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 14/24719-7 - Efeito do exercício físico sobre a modulação da expressão do receptor ativado por proliferadores de peroxissomos gama (PPARgama) e da Insulin Degrading Enzyme em ilhotas pancreáticas de camundongos
• Beneficiário: Mirian Ayumi Kurauti
• Modalidade de apoio: Bolsas no Brasil - Doutorado