Abstract:
Amyloidosis forms a large family of pathologies associated with amyloid deposit generated by the formation of amyloid fibrils or plaques. The amyloidogenic proteins and peptides involved in these processes are targeted against almost all organs. In brain they are associated with neurodegenerative disease, and the Translocator Protein (TSPO), overexpressed in these inflammatory conditions, is one of the target for the diagnostic. Moreover, TSPO ligands have been described as promising therapeutic drugs for neurodegenerative diseases. Type 2 diabetes, another amyloidosis, is due to a beta cell mass decrease that has been linked to hIAPP (human islet amyloid polypeptide) fibril formation, leading to the reduction of insulin production. In the present study, in a first approach, we link overexpression of TSPO and inflammation in potentially prediabetic patients. In a second approach, we observed that TSPO deficient rats have higher level of insulin secretion in basal conditions and more IAPP fibrils formation compared with wild type animals. In a third approach, we show that diabetogenic conditions also increase TSPO overexpression and IAPP fibril formation in rat beta pancreatic cell line (INS-1E). These data open the way for further studies in the field of type 2 diabetes treatment or prevention.
摘要:
淀粉样变性形成与淀粉样原纤维或斑块形成所产生的淀粉样蛋白沉积相关的病理大家族。参与这些过程的淀粉样蛋白和肽几乎靶向所有器官。在大脑中,它们与神经退行性疾病相关,和转运蛋白(TSPO),在这些炎症中过度表达,是诊断的目标之一。此外,TSPO配体已被描述为用于神经退行性疾病的有希望的治疗药物。2型糖尿病,另一个淀粉样变性,是由于与hIAPP(人胰岛淀粉样多肽)原纤维形成有关的β细胞质量减少,导致胰岛素产量减少。在本研究中,在第一种方法中,我们将TSPO的过度表达与潜在糖尿病前期患者的炎症联系起来.在第二种方法中,我们观察到,与野生型动物相比,TSPO缺陷大鼠在基础条件下具有更高的胰岛素分泌水平和更多的IAPP原纤维形成。在第三种方法中,我们表明,在大鼠β胰腺细胞系(INS-1E)中,致糖尿病的条件也会增加TSPO过表达和IAPP原纤维的形成。这些数据为2型糖尿病治疗或预防领域的进一步研究开辟了道路。