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首页> 外文期刊>Cellular Physiology and Biochemistry >Insulin Influences Autophagy Response Distinctively in Macrophages of Different Compartments
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Insulin Influences Autophagy Response Distinctively in Macrophages of Different Compartments

机译：胰岛素在不同隔室的巨噬细胞中显着影响自噬反应。

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biBackground/Aims /i/bDiabetes mellitus (DM) is characterized by hyperglycemia, associated to a lack or inefficiency of the insulin to regulate glucose metabolism. DM is also marked by alterations in a diversity of cellular processes that need to be further unraveled. In this study, we examined the autophagy pathway in diabetic rat macrophages before and after treatment with insulin. biMethods /i/bBone marrow-derived macrophages (BMM), bronchoalveolar lavage (BAL) and splenic tissue of diabetic male Wistar rats (alloxan, 42 mg/kg, i.v., 10 days) and control rats (physiological saline, i.v.). Some diabetic rats were given neutral protamine Hagedorn insulin (4 IU, s.c.) 8 h before experiments. For characterization of the model and evaluation of the effect of insulin on the autophagic process, the following analyzes were performed (a) concentrations of cytokines interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6, IL-4, IL-10, cytokine-induced neutrophil chemoattractant (CINC)-1 and CINC-2 in the BAL supernatant was measured by ELISA; (b) characterization of alveolar macrophage (AM) of the BAL as surface antigens (MHCII, pan-macrophage KiM2R, CD11b) and autophagic markers (protein microtubule-associated light chain (LC)3, autophagy protein (Atg)12 by flow cytometry and confocal microscopy (c) study of macrophages differentiated from the bone marrow by flow cytometry and confocal microscopy (d) histology of the spleen by immunohistochemistry associated with confocal microscopy. biResults /i/bInterestingly, insulin exerted antagonistic effects on macrophages from different tissues. Macrophages from bronchoalveolar lavage (BAL) enhanced their LC3 autophagosome bound content after treatment with insulin whereas splenic macrophages from red pulp in diabetic rats failed to enhance their Atg 12 levels compared to control animals. Insulin treatment in diabetic rats did not change LC3 content in bone marrow derived macrophages (BMM). M1 and M2 macrophages behaved accordingly to the host they were derived from. Diabetic M1 BMM had their LC3 vesicle-bound content diminished and M2 BMM enhanced their LC3 levels and insulin treatment failed to rescue autophagy to control levels. Insulin normalizes CINC-2 level but does not modulate autophagy markers. biConclusion /i/bTaking these results together, diabetic macrophages derived from different compartments show different levels of autophagy markers compared to healthy animals, therefore, they suffer distinctively in the absence of insulin.
机译：背景/目标 糖尿病（DM）的特点是高血糖症，与胰岛素调节葡萄糖代谢的缺乏或效率低下有关。 DM的特征还在于需要进一步阐明的多种细胞过程的变化。在这项研究中，我们检查了胰岛素治疗前后糖尿病大鼠巨噬细胞的自噬途径。 方法 糖尿病雄性Wistar大鼠的骨髓衍生巨噬细胞（BMM），支气管肺泡灌洗（BAL）和脾组织（四氧嘧啶，42 mg / kg，静脉注射，第10天）和对照大鼠（生理盐水，iv）。在实验前8小时，一些糖尿病大鼠接受了中性鱼精蛋白Hagedorn胰岛素（4 IU，皮下注射）。为了表征模型并评估胰岛素对自噬过程的影响，进行了以下分析：（a）细胞因子白介素（IL）-1β，肿瘤坏死因子（TNF）-α，IL-6，IL- 4，用ELISA法测定BAL上清液中IL-10，细胞因子诱导的中性粒细胞趋化因子（CINC）-1和CINC-2。 （b）通过流式细胞术将BAL的肺泡巨噬细胞（AM）表征为表面抗原（MHCII，泛巨噬细胞KiM2R，CD11b）和自噬标记（蛋白微管相关轻链（LC）3，自噬蛋白（Atg）12）和共聚焦显微镜（c）通过流式细胞术和共聚焦显微镜研究巨噬细胞与骨髓的分化（d）与共聚焦显微镜相关的免疫组织化学研究脾脏的组织学 结果 胰岛素对不同组织的巨噬细胞产生拮抗作用，胰岛素治疗后，支气管肺泡灌洗（BAL）巨噬细胞增加了其LC3自噬体结合含量，而糖尿病大鼠红髓脾脏巨噬细胞与对照组相比则未能提高其Atg 12水平。糖尿病大鼠的治疗没有改变骨髓源巨噬细胞（BMM）中LC3的含量，M1和M2巨噬细胞的行为与其来源的宿主相符。 ic M1 BMM的LC3囊泡结合含量减少，M2 BMM增强了LC3水平，胰岛素治疗未能将自噬恢复至对照水平。胰岛素可使CINC-2水平正常化，但不会调节自噬标记物。 结论 综上所述，与健康动物相比，来自不同区室的糖尿病巨噬细胞显示出不同水平的自噬标志物，因此，它们在没有胰岛素的情况下会遭受明显的痛苦。

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