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.

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As lesões histopatológicas observadas no fígado de 12 cavalos de procedências diversas, descritas neste trabalho, sugerem a interferência de um mesmo agente etiológico, possìvelmente uma intoxicação crônica provocada pela infestão de vegetais do gen. Senecio ou de plantas contendo alcalóides afins. Nota: - Já estava redigido o presente trabalho, quando deparamos com o artigo de VANEK (Vanek, J., 1958), Vergiftung mit Kreuskraut (Senecio) als ursache der Zdárer Pferdseuche. - Schveiz. Z. Allg. Path. Bakt., 21:821-848), onde o autor, baseado em dados clínicos, anatõmicos, botânicos, toxicológicos e experimentais, conclui que a doença dos cavalos de Zdar é devida a uma intoxicação crônica pelos alcalóides do Senecio erraticus ssp. barbaraeifolius. As alterações histopatológicas descritas no referido trabalho, coincidem com as observadas nos nossos casos

These findings show that Respiratory Syncytial Virus infection contributes to Th1 polarisation in immune response of respiratory mucosa, an effect that is similar to other environmental factors. Further studies are needed to assess immune response to other infectious causes of acute bronchiolitis.