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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Guimaraes, Joao Pedro Torres [1, 2] ; Filgueiras, Luciano Ribeiro [2] ; Martins, Joilson Oliveira [1] ; Jancar, Sonia [2]
Total Authors: 4
[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
Total Affiliations: 2
Document type: Journal article
Source: Mediators of Inflammation; 2019.
Web of Science Citations: 0

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)

FAPESP's process: 13/15719-0 - Association of receptors for lipid mediators with PRRs in macrophages and dendritic cells
Grantee:Sônia Jancar
Support type: Research Projects - Thematic Grants
FAPESP's process: 17/11540-7 - Investigating the role of insulin in the presence of allergic pulmonary inflammation in diabetic and healthy mice
Grantee:Joilson de Oliveira Martins
Support type: Regular Research Grants