Expression Pattern of 12-Lipoxygenase in Human Islets With Type 1 Diabetes and Type 2 Diabetes
Expression Pattern of 12-Lipoxygenase in Human Islets With Type 1 Diabetes and Type 2 Diabetes
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DOI：
10.1210/jc.2014-3630
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发表时间：
2015-03-01
影响因子：
5.8
通讯作者：
Morris, Margaret A.
中科院分区：
文献类型：
--
作者：
Grzesik, Wojciech J.;Nadler, Joseph L.;Morris, Margaret A.
背景：胰腺的炎症会引起β细胞压力，导致糖尿病的发展。通过糖尿病胰腺器官供体网络（nPOD）进入人类胰腺组织，可以表征导致这种炎症的途径。目的：12-脂氧合酶（12-LO）诱导炎症并参与糖尿病的发展。我们的目的是确定12-LO在对照、自身抗体阳性、1型糖尿病和2型糖尿病非pod胰腺供者胰岛中的表达。设计：采用免疫组织化学和免疫荧光法检测nPOD供体胰腺组织中不同亚群胰岛细胞中12-LO的表达。参与者：根据疾病状况从nPOD中获得供体胰腺样本（对照组，n = 7；自身抗体阳性，n = 8； 1型糖尿病，n = 17；或2型糖尿病供体，n = 15）。主要结局指标：测定人胰岛内12-LO的表达作为主要结局指标，包括区分哪些类型的胰岛细胞表达12-LO。结果：对照组（非糖尿病患者）胰岛缺乏12-LO的表达。在其他组的供体中，25%至37%的供体表达胰岛12-LO，在12-LO+病例的胰岛中β细胞和12-LO+细胞的数量之间存在明显的反比关系。巨噬细胞、内皮细胞、α细胞或β细胞中均未见12-LO表达，仅在表达低水平胰多肽（PP）和高水平波形蛋白的细胞中可见。结论：在糖尿病前期和糖尿病条件下，12-LO表达共定位于一种特定类型的胰岛PP+细胞。PP和vimentin的表达表明12-LO参与了胰岛β细胞去分化的过程。
Context: Inflammation in the pancreas can cause beta-cell stress, leading to diabetes development. Access to human pancreas tissues via the Network for Pancreatic Organ Donors with Diabetes (nPOD) has allowed characterization of pathways leading to this inflammation.Objective: 12-Lipoxygenase (12-LO) induces inflammation and has been implicated in diabetes development. Our goal was to determine expression of 12-LO in human islets from control, autoantibody- positive, type 1 diabetic, and type 2 diabetic nPOD pancreas donors.Design: Pancreas tissues from nPOD donors were examined by immunohistochemistry and immunofluorescence for islet expression of 12-LO in different subsets of islet cells.Participants: Donor pancreas samples were obtained from nPOD based on disease status (control, n = 7; autoantibody-positive, n = 8; type 1 diabetic, n = 17; or type 2 diabetic donors, n = 15). Main Outcome Measure: Determination of 12-LO expression within human islets served as the main outcome measure, including distinguishing which types of islet cells expressed 12-LO.Results: Islets from control participants (nondiabetic) lacked islet expression of 12-LO. Of donors in the other groups, 25% to 37% expressed islet 12-LO with a clear inverse relation between the numbers of beta-cells and 12-LO+ cells within islets of 12-LO+ cases. 12-LO expression was not seen within macrophages, endothelial cells, alpha-cells, or beta-cells, but only within cells expressing low levels of pancreatic polypeptide (PP) and increased levels of vimentin.Conclusions: 12-LO expression colocalizes within a specific type of islet PP+ cell under prediabetic and diabetic conditions. The costaining of PP and vimentin suggests that 12-LO participates in the process leading to beta-cell dedifferentiation in the islet.