Boom Alain, Lybaert Pascale, Pollet Jean-François, Jacobs Paul, Jijakli Hassan, Golstein Philippe E, Sener Abdullah, Malaisse Willy J, Beauwens Renaud
Laboratory of Histology, Neuroanatomy and Neuropathology, School of Medicine, Université Libre de Bruxelles, CP 620, 808, route de Lennik, 1070, Brussels, Belgium.
Endocrine. 2007 Oct;32(2):197-205. doi: 10.1007/s12020-007-9026-x. Epub 2007 Nov 27.
Impaired glucose tolerance and overt diabetes mellitus are becoming increasingly common complications of cystic fibrosis (CF), most probably merely as a result of increased life expectancy. In order to understand the pathophysiology of cystic fibrosis-related diabetes (CFRD), knowledge on the possible expression and cell distribution of the cystic fibrosis transmembrane conductance regulator (CFTR) protein within the endocrine pancreas is required. In this report, we establish the first evidence for expression of CFTR protein in rat pancreatic islets by using independent techniques. First reverse transcriptase-polymerase chain reaction (RT-PCR) amplification showed that CFTR mRNA is present in isolated islets of Langerhans. Furthermore, the analysis of flow cytometry-separated islet cells indicated that the level of CFTR transcripts is significantly higher in the non-beta than in beta-cell populations. The expression of CFTR protein in rat islet cells was also demonstrated by Western blotting and the level of expression was also found significantly higher in the non-beta than in beta-cell populations. Last, in situ immunocytochemistry studies with two monoclonal antibodies recognizing different CFTR epitopes indicated that CFTR expression occurs mainly in glucagon-secreting alpha-cells.
糖耐量受损和显性糖尿病正日益成为囊性纤维化(CF)常见的并发症,这很可能仅仅是预期寿命增加的结果。为了了解囊性纤维化相关糖尿病(CFRD)的病理生理学,需要了解囊性纤维化跨膜传导调节因子(CFTR)蛋白在内分泌胰腺中的可能表达和细胞分布情况。在本报告中,我们通过使用独立技术首次证实了CFTR蛋白在大鼠胰岛中的表达。首先,逆转录聚合酶链反应(RT-PCR)扩增显示,CFTR mRNA存在于分离的胰岛中。此外,对流式细胞术分离的胰岛细胞的分析表明,CFTR转录本在非β细胞群体中的水平显著高于β细胞群体。Western印迹也证实了CFTR蛋白在大鼠胰岛细胞中的表达,并且在非β细胞群体中的表达水平也显著高于β细胞群体。最后,使用两种识别不同CFTR表位的单克隆抗体进行的原位免疫细胞化学研究表明,CFTR表达主要发生在分泌胰高血糖素的α细胞中。