Reddy S, Young M, Poole C A, Ross J M
Department of Paediatrics, University of Auckland School of Medicine, New Zealand.
Gen Comp Endocrinol. 1998 Jul;111(1):9-19. doi: 10.1006/gcen.1998.7079.
Glucose transporter-2 (glut2) is underexpressed in beta cells of several rodent models of non-insulin-dependent diabetes mellitus (NIDDM). This may also be true for rodent models of insulin-dependent diabetes mellitus (IDDM). The present study examines two murine models of autoimmune IDDM, the nonobese diabetic (NOD) and the low-dose streptozotocin (stz) murine models for changes in the expression of glut2 by double-label light and confocal microscopy during various stages of the disease. The spatial distribution of glut2 cells was also examined in relation to insulin immunoreactive cells and the islet inflammatory cells during these stages. In both the female NOD mouse and the female Swiss mouse without stz treatment, glut2 colocalized with insulin in virtually all the beta cells. In the NOD mouse, islets with moderate to advanced insulitis showed either an absence or considerably reduce expression of glut2 in insulin-containing beta cells. Cells with reduced glut2 expression were usually located adjacent to the region of insulitis. At onset of diabetes, glut2 immunolabeling was reduced despite the preservation of weak insulin immunoreactivity. In Swiss mice treated repeatedly with stz, glut2 labeling began to decline in select Beta cells after the fourth injection in approximately 50% of the islets, despite the lack of insulitis. At this stage expression of glut2 fell in a small number of islets with evidence of early macrophage infiltration. Loss of glut2 became more pronounced in nondiabetic Swiss mice after the fifth injection. At this stage glut2 labeling in the plasma membrane appeared diffuse and variable. At onset of stz-induced diabetes, glut2 expression significantly fell, despite weak immunoreactivity for insulin. This loss was associated with an enhanced influx of both macrophages and T lymphocytes within the islets of diabetes mice. In both the NOD and the low-dose stz mouse models, loss of glut2 thus occurs from an early stage and precedes hyperglycaemia. This loss may be mediated by immune and nonimmune mechanisms.
葡萄糖转运蛋白2（glut2）在几种非胰岛素依赖型糖尿病（NIDDM）啮齿动物模型的β细胞中表达不足。这在胰岛素依赖型糖尿病（IDDM）啮齿动物模型中可能也是如此。本研究通过双标记光镜和共聚焦显微镜检查了两种自身免疫性IDDM小鼠模型，即非肥胖糖尿病（NOD）和低剂量链脲佐菌素（stz）小鼠模型在疾病不同阶段glut2表达的变化。还检查了这些阶段glut2细胞与胰岛素免疫反应性细胞和胰岛炎性细胞相关的空间分布。在未经stz处理的雌性NOD小鼠和雌性瑞士小鼠中，几乎所有β细胞中的glut2都与胰岛素共定位。在NOD小鼠中，中度至重度胰岛炎的胰岛显示含胰岛素的β细胞中glut2表达缺失或显著降低。glut2表达降低的细胞通常位于胰岛炎区域附近。在糖尿病发病时，尽管保留了微弱的胰岛素免疫反应性，但glut2免疫标记减少。在用stz反复处理的瑞士小鼠中，尽管没有胰岛炎，但在第四次注射后，约50%的胰岛中选定的β细胞中glut2标记开始下降。在此阶段，少数有早期巨噬细胞浸润迹象的胰岛中glut2表达下降。第五次注射后，非糖尿病瑞士小鼠中glut2的丧失更为明显。在此阶段，质膜中的glut2标记显得弥散且多变。在stz诱导的糖尿病发病时，尽管胰岛素免疫反应性较弱，但glut2表达显著下降。这种丧失与糖尿病小鼠胰岛内巨噬细胞和T淋巴细胞的流入增加有关。因此，在NOD和低剂量stz小鼠模型中，glut2的丧失都从早期开始，并先于高血糖症出现。这种丧失可能由免疫和非免疫机制介导。
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