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Title: IRS-1 pY612 and Akt-1/PKB pT308 Phosphorylation and Antiinflammatory Effect of Diindolylmethane in Adipocytes Cocultured with Macrophages
Authors: López Vázquez, Alfonso
García Bañuelos, Jesús Javier
González Garibay, Angélica Sofía
Urzúa Lozano, Pedro Ernesto
Del Toro Arreola, Susana
Bueno Topete, Miriam Ruth
Sánchez Enríquez, Sergio
Muñoz Valle, José Francisco
Jave Suárez, Luis Felipe
Armendáriz Borunda, Juan Socorro
Bastidas Ramírez, Blanca Estela
Keywords: diabetes mellitus type 2
insulin resistance
insulin signaling pathway
Issue Date: Dec-2017
Publisher: Bentham Science
Citation: Lopez-Vazquez A. Garcia-Banuelos JJ *, Gonzalez-Garibay AS, Urzua-Lozano PE, Del Toro-Arreola S, Bueno-Topete MR, Sanchez-Enriquez S, Munoz-Valle JF, Jave-Suarez LF, Armendariz-Borunda J and Bastidas-RamireZ BE. (2017). IRS-1 pY612 and Akt-1/PKB pT308 Phosphorylation and Antiinflammatory Effect of Diindolylmethane in Adipocytes Cocultured with Macrophages. Medicinal Chemistry, Vol. 13, Issue 8. 727-733 pp. DOI: 10.2174/1573406413666170922095011
Series/Report no.: Medicinal Chemistry;Volume 13, Issue 8 , December 2017
Abstract: 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-B, 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 M, 40 M and 60 M DIM for 24 h followed by 100 nM insulin for 20 min. MCP-1, IL-6 and TNF 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 TNF 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.
Description: Artículo
ISSN: 1875-533X online
0929-8673 print
DOI: 10.2174/1573406413666170922095011
Appears in Collections:3209 Artículos

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