Roles of various types of glucose transporter gene in diabetes mellitus

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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