Roles of various types of glucose transporter gene in diabetes mellitus

我们以前曾报道过GLUT 2的基因表达受周围葡萄糖浓度的调节，并且在某些条件下，GLUT 2可能成为葡萄糖诱导的胰腺β细胞胰岛素分泌的调节剂。Goto-Kakizaki大鼠（GK大鼠）是已知的非胰岛素依赖型糖尿病（NIDDM）的遗传动物模型，并且在使用灌流的大鼠胰腺和分离的胰岛的体外实验中观察到葡萄糖诱导的胰岛素分泌被选择性地损害。另一方面，精氨酸刺激的胰岛素分泌没有受损，并且该动物模型的胰岛素分泌的特征类似于人NIDDM患者的胰岛素分泌的特征。GK大鼠胰岛中GLUT 2 mRNA含量降低至正常胰岛的60 - 70%水平，免疫组化研究也显示GK大鼠胰腺β细胞中GLUT 2蛋白减少。 ...更多信息 在其他胰腺a、d和PP细胞中未检测到GLUT 2蛋白。然而，已经证明，GLUT 2中的葡萄糖转运能力很大，并且仅5 - 10%的GLUT 2蛋白含量就足以进行正常的转运活性。因此，我们很难断定GK大鼠胰岛β细胞中GLUT 2基因和蛋白质含量的减少是导致该动物模型中葡萄糖诱导的胰岛素分泌选择性受损的主要原因，可能存在其他可能性，即GLUT 2基因/蛋白质结构异常与胰岛β细胞葡萄糖转运功能障碍有关。为了筛选这种异常，我们使用聚合酶链反应-单链构象多态性（SSPC）技术。然而，我们还没有获得异常条带的GLUT 2的PCR产物从外显子1至9。目前认为GLUT 2基因第1 ~ 9外显子的结构异常与NIDDM的发病无关，但SSPC是筛查NIDDM患者GLUT 2基因异常的有效方法。少

We have previously reported that the gene expression of GLUT2 is regulated by the ambient glucose concentration and that there might be the possibility that GLUT2 become a regulator of glucose-induced insulin secretion from pancreatic beta cells under some conditions. Goto-Kakizaki rat (GK rat)is known to be a genetic animal model of non-insulin-dependent diabetes mellitus (NIDDM), and the glucose-induced insulin secretion is observed to be selectively impaired in both of the in vitro experiments using the perfused rat pancreas and the isolated pancreatic islets. On the other hand, the insulin secretion by arginine stimulation is not impaired, and the characteristic features of insulin secretion of this animal model is akin to those of human NIDDM patients. The GLUT2 mRNA contents in pancreatic isles in GK rats are decreased to the level of 60 - 70 % of normal islets, and the immunohistochemical study also reveals that the GLUT2 protein is decreased in pancreatic beta cells of GK rats. … More The GLUT2 protein is not detected in other pancreatic a, d and PP cells. It has been demonstrated, however, that the capacity of glucose transport in GLUT2 is large and that only 5 - 10 % of GLUT2 protein content is sufficient for the normal transport activity. Therefore, it seems to be difficult to conclude that the reduced mRNA and protein content in beta cells of GK rats is the major contributor of the selective impairment of glucoseinduced insulin secretion in this animal model.There might be other possibility that the structural abnormality of GLUT2 gene/protein is related to the malfunction of glucose transport in pancreatic beta cells. To screen this abnormality, we used the technique of polymerase chain reaction-single stranded conformation polymorphism (SSPC). However, we have not yet obtain the abnormal band of GLUT2 PCR products from exon 1 to 9. The structural abnormalities of GLUT2 gene from exon 1 to 9 is thought to be not related to the pathogenesis of NIDDM at this time, although SSPC is a useful method for screening of the gene abnormality of GLUT2 in NIDDM patients. Less