Yamauchi Masahiro, Sudo Kaori, Ito Hidenori, Iwamoto Ikuko, Morishita Rika, Murai Toshihiro, Kajita Kazuo, Ishizuka Tatsuo, Nagata Koh-ichi
Department of General Internal Medicine, Gifu University School of Medicine, Gifu, Japan.
Med Mol Morphol. 2013 Mar;46(1):41-8. doi: 10.1007/s00795-013-0008-1. Epub 2013 Jan 17.
We have shown that two multidomain adaptor proteins, p140Cap and vinexin, interact with each other and are likely to be involved in neurotransmitter release. Because the basic molecular mechanism governing neurotransmitter and insulin secretion is conserved, these two proteins may also to play pivotal roles in insulin secretion. We therefore performed some characterization of p140Cap and vinexin in pancreas of a wild-type rat or a spontaneous type 2 diabetes mellitus (DM) model, the Otsuka Long-Evans Tokushima Fatty (OLETF) rat. These two proteins were detected in Wistar rat pancreas by Western blotting. Immunohistochemistry revealed that p140Cap and vinexin are enriched in β and α cells, respectively, in the rat pancreas. We then found that pancreatic islet structure was disorganized in the OLETF rat with hyperinsulinemia or with hyperglycemia, based on immunohistochemical analyses of vinexin. In β cells of these model rats, p140Cap was distributed in a cytoplasmic granular pattern as in the control rats, although its expression was reduced to various extents from cell to cell. These results may suggest possible involvement of p140Cap in insulin secretion, and reduction of p140Cap might be related to abnormal insulin secretion in DM.
我们已经表明,两种多结构域衔接蛋白p140Cap和葡萄肌动蛋白相互作用,并且可能参与神经递质释放。由于控制神经递质和胰岛素分泌的基本分子机制是保守的,这两种蛋白可能在胰岛素分泌中也起关键作用。因此,我们对野生型大鼠或自发性2型糖尿病(DM)模型大冢长-艾氏-德岛肥胖(OLETF)大鼠胰腺中的p140Cap和葡萄肌动蛋白进行了一些特性分析。通过蛋白质印迹法在Wistar大鼠胰腺中检测到这两种蛋白。免疫组织化学显示,在大鼠胰腺中,p140Cap和葡萄肌动蛋白分别在β细胞和α细胞中富集。然后,基于对葡萄肌动蛋白的免疫组织化学分析,我们发现患有高胰岛素血症或高血糖症的OLETF大鼠的胰岛结构紊乱。在这些模型大鼠的β细胞中,p140Cap像对照大鼠一样以细胞质颗粒模式分布,尽管其表达在不同细胞间有不同程度的降低。这些结果可能表明p140Cap可能参与胰岛素分泌,并且p140Cap的减少可能与DM中异常的胰岛素分泌有关。