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IRS-1 pY612 and Akt-1/PKB pT308 Phosphorylation and Antiinflammatory Effect of Diindolylmethane in Adipocytes Cocultured with Macrophages

[ Vol. 13 , Issue. 8 ]

Author(s):

Alfonso Lopez-Vazquez, Jesus J. Garcia-Banuelos*, Angelica S. Gonzalez-Garibay, Pedro E. Urzua-Lozano, Susana Del Toro-Arreola, Miriam R. Bueno-Topete, Sergio Sanchez-Enriquez, Jose F. Munoz-Valle, Luis F. Jave-Suarez, Juan Armendariz-Borunda and Blanca E. Bastidas-Ramirez*   Pages 727 - 733 ( 7 )

Abstract:


Background: 3,3'-Diindolylmethane (DIM) is a condensation product of indole-3-carbinol, a glucosinolate naturally occurring in Brassica genus vegetables. The antiinflammatory properties of DIM through the inhibition of NF-κB, as well as its ameliorating effects on glucose tolerance and hyperglicemic states, have been described. A subclinical proinflammatory profile resultant from the interaction of adipocytes and macrophages has been reported in obesity, affecting the insulin signaling pathway, contributing to insulin resistance.

Objective: The aim of this study was to evaluate the effect of DIM on proinflammatory cytokines and phosphorylation of IRS-1 pY612 and Akt-1/PKB pT308 in an obesity-induced inflammation model.

Methods: Differentiated 3T3-L1 adipocytes were co-cultured with RAW 264.7 macrophages and exposed to 20 µM, 40 µM and 60 µM DIM for 24 h followed by 100 nM insulin for 20 min. MCP-1, IL-6 and TNFα were quantified in the supernatant through individual ELISAs. Adipocyte lysates were used to determine the relative expression of the proinflammatory mediators by qPCR, and the phosphorylation of IRS-1 pY612 and Akt-1/PKB pT308 proteins by western blot analysis.

Results: DIM significantly (p<0.05) reduced the production and mRNA expression of MCP-1, IL-6, and TNFα in a DIM concentration dependent manner, concomitantly increasing the abundance of IRS-1 pY612 and Akt-1/PKB pT308.

Conclusion: Our results suggest that DIM influences the insulin transduction pathway by exerting an antiinflammatory effect. The potential therapeutic benefits of DIM in the treatment of glucose metabolic disorders deserve further studies.

Keywords:

Diabetes mellitus type 2, glucose, inflammation, insulin resistance, insulin signaling pathway, obesity, phytochemicals.

Affiliation:

Instituto de Investigacion en Enfermedades Cronico Degenerativas, Departamento de Biologia Molecular y Genomica, Universidad de Guadalajara, Guadalajara, Jalisco, Instituto de Biologia Molecular en Medicina y Terapia Genica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, puerta 7, 3er. piso, Calle Sierra Mojada # 950, Col. Independencia, Guadalajara, Jalisco, C.P. 44340, Instituto de Investigacion en Enfermedades Cronico Degenerativas, Departamento de Biologia Molecular y Genomica, Universidad de Guadalajara, Guadalajara, Jalisco, Instituto de Investigacion en Enfermedades Cronico Degenerativas, Departamento de Biologia Molecular y Genomica, Universidad de Guadalajara, Guadalajara, Jalisco, Instituto de Investigacion en Enfermedades Cronico Degenerativas, Departamento de Biologia Molecular y Genomica, Universidad de Guadalajara, Guadalajara, Jalisco, Instituto de Investigacion en Enfermedades Cronico Degenerativas, Departamento de Biologia Molecular y Genomica, Universidad de Guadalajara, Guadalajara, Jalisco, Laboratorio de Bioquimica, Departamento de Biologia Molecular y Genomica, Universidad de Guadalajara, Guadalajara, Jalisco, Instituto de Investigacion en Ciencias Biomedicas, Departamento de Biologia Molecular y Genomica, Universidad de Guadalajara, Guadalajara, Jalisco, Centro de Investigacion Biomedica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, Instituto de Biologia Molecular en Medicina y Terapia Genica, Departamento de Biologia Molecular y Genomica, Universidad de Guadalajara, Guadalajara, Jalisco, Instituto de Investigacion en Enfermedades Cronico Degenerativas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, puerta 7, 2do. piso., Calle Sierra Mojada # 950, Col. Independencia, Guadalajara, Jalisco, C.P. 44340

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