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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Leukotriene Involvement in the Insulin Receptor Pathway and Macrophage Profiles in Muscles from Type 1 Diabetic Mice

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Autor(es):
Guimaraes, Joao Pedro Torres [1, 2] ; Filgueiras, Luciano Ribeiro [2] ; Martins, Joilson Oliveira [1] ; Jancar, Sonia [2]
Número total de Autores: 4
Afiliação do(s) autor(es):
[1] Univ Sao Paulo FCF USP, Lab Immunoendocrinol, Dept Clin & Toxicol Anal, Sch Pharmaceut Sci, Sao Paulo - Brazil
[2] Univ Sao Paulo ICB USP, Lab Immunopharmacol, Dept Immunol, Inst Biomed Sci, Sao Paulo - Brazil
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: Mediators of Inflammation; 2019.
Citações Web of Science: 0
Resumo

Type 1 diabetes (T1D) is a metabolic disease associated with systemic low-grade inflammation and macrophage reprogramming. There is evidence that this inflammation depends on the increased systemic levels of leukotriene (LT) B4 found in T1D mice, which shifts macrophages towards the proinflammatory (M1) phenotype. Although T1D can be corrected by insulin administration, over time T1D patients can develop insulin resistance that hinders glycemic control. Here, we sought to investigate the role of leukotrienes (LTs) in a metabolically active tissue such as muscle, focusing on the insulin signaling pathway and muscle-associated macrophage profiles. Type 1 diabetes was induced in the 129/SvE mouse strain by streptozotocin (STZ) in mice deficient in the enzyme responsible for LT synthesis (5LO(-/-)) and the LT-sufficient wild type (WT). The response to insulin was evaluated by the insulin tolerance test (ITT), insulin concentration by ELISA, and Akt phosphorylation by western blotting. The gene expression levels of the insulin receptor and macrophage markers Stat1, MCP-1, Ym1, Arg1, and IL-6 were evaluated by qPCR, and that of IL-10 by ELISA. We observed that after administration of a single dose of insulin to diabetic mice, the reduction in glycemia was more pronounced in 5LO(-/-) than in WT mice. When muscle homogenates were analyzed, diabetic 5LO(-/-) mice showed a higher expression of the insulin receptor gene and higher Akt phosphorylation. Moreover, in muscle homogenates from diabetic 5LO(-/-) mice, the expression of anti-inflammatory macrophage markers Ym1, Arg1, and IL-10 was increased, and the relative expression of the proinflammatory cytokine IL-6 was reduced compared with WT diabetic mice. These results suggest that LTs have an impact on the insulin receptor signaling pathway and modulate the inflammatory profile of muscle-resident macrophages from T1D mice. (AU)

Processo FAPESP: 17/11540-7 - Investigando o papel da insulina na vigência da inflamação alérgica pulmonar em camundongos diabéticos e sadios
Beneficiário:Joilson de Oliveira Martins
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 13/15719-0 - Associação de PRRs com receptores para mediadores lipídicos em macrófagos e células dendríticas
Beneficiário:Sônia Jancar
Linha de fomento: Auxílio à Pesquisa - Temático