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Pancreas Pathology of Latent Autoimmune Diabetes in Adults (LADA) in Patients and in a LADA Rat Model Compared to Type 1 Diabetes Mellitus
Diabetes ( IF 6.2 ) Pub Date : 2020-01-23 , DOI: 10.2337/db19-0865
Anne Jörns 1 , Dirk Wedekind 2 , Joachim Jähne 3 , Sigurd Lenzen 4, 5
Affiliation  

Around 10% of type 2 diabetes patients suffer from latent autoimmune diabetes in adults (LADA). This study provides a systematic assessment of the pathology of the endocrine pancreas of patients with LADA and for comparison in a first rat model miming the characteristics of LADA patients. Islets in human and rat pancreases were analyzed by immunohistochemistry for immune cell infiltrate composition, by in situ RT- PCR and qRT-PCR of laser microdissected islets for gene expression of pro-inflammatory cytokines, the proliferation marker PCNA, the anti-inflammatory cytokine IL-10 and the apoptosis markers caspase 3 and TUNEL. Human and rat LADA pancreases showed differences in areas of the pancreas with respect to immune cell infiltration and a changed ratio between the number of macrophages and CD8 T-cells towards macrophages in the islet infiltrate. Gene expression analyses revealed a changed ratio due to an increase of IL-1β and a decrease of TNF-α. IL-10 and PCNA expression were increased in the LADA situation, while caspase 3 gene expression was reduced. The analyses into the underlying pathology in human as well as rat LADA pancreases provided identical results allowing the conclusion that LADA is a milder form of autoimmune diabetes in patients of an advanced age.

中文翻译:

与 1 型糖尿病相比,患者和 LADA 大鼠模型中成人潜伏性自身免疫性糖尿病 (LADA) 的胰腺病理学

大约 10% 的 2 型糖尿病患者患有成人潜伏性自身免疫性糖尿病 (LADA)。该研究提供了对 LADA 患者内分泌胰腺病理学的系统评估,并在模拟 LADA 患者特征的第一个大鼠模型中进行了比较。通过免疫组织化学分析人和大鼠胰岛中的免疫细胞浸润成分,通过激光显微切割胰岛的原位 RT-PCR 和 qRT-PCR 分析促炎细胞因子、增殖标志物 PCNA、抗炎细胞因子 IL 的基因表达-10 和凋亡标志物 caspase 3 和 TUNEL。人和大鼠 LADA 胰腺在免疫细胞浸润方面表现出胰腺区域的差异,以及胰岛浸润中巨噬细胞和 CD8 T 细胞对巨噬细胞的比例变化。基因表达分析显示,由于 IL-1β 的增加和 TNF-α 的减少,比率发生了变化。在 LADA 情况下,IL-10 和 PCNA 表达增加,而 caspase 3 基因表达减少。对人类和大鼠 LADA 胰腺潜在病理学的分析提供了相同的结果,从而得出结论,LADA 是老年患者的一种较轻的自身免疫性糖尿病。
更新日期:2020-01-23
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