Studies on molecular mechanism of etiology of diabetes mellitus

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In order to investigate the regulation of glucose transporter gene expression in the altered metabolic conditions of diabetes, we have measured MRNA levels encoding GLUT4 in the liver and GLUT4 in the gastrocnemius muscle from various insulin resistant animal models, including Zucker fatty, Wistar fatty, and streptozocin(STZ)-treated diabetic rats. Northern blot analysis revealed that GLUT2 MRNA levels were significantly(P<0.001)elevated in 14 wk Zucker fatty and Wistar fatty rats relative to lean littermates but were similar in these two groups at 5 wk of age. Furthermore, there was significant increase(P<0.01)in GLUT2 MRNA levels in STZ diabetic rats at 3 wk after treatment. GLUT4 MRNA levels were not significantly different between control and insulin resistant rats in all animal models. These results indicate that neither hyperinsulinemia nor hyperglycemia affects GLUT4 MRNA levels in the muscle. However, GLUT2 MRNA levels in the liver were elevated in obesity and diabetes, althoug … More h this regulatory event occurred independently from circulating insulin or glucose concentrations. On the other hand, previous studies revealed that rat islets express the GLUT2-liver facilitative glucose transporter isoform, a glucose carrier with a low affinity for glucose but a high capacity for glucose transport. These studies indicated the presence of a second glucose transporter in rat islets ; however, they did not indicate to which of the five known facilitative glucose transporters it corresponded. In this study, we isolated RNA from rat islets of Langerhans and confirmed the presence of GLUT2 MRNA. In addition, we present data indicating that the second isoform expressed in islets is the GLUTI-erythrocyte isoform. The effect of culturing islets in 5.5, 8.3 or 11.1 mM glucose on the levels of GLUT1 and GLUT2 MRNA also was examined. The levels of GLUTI and GLUT2 MRNA were two- and threefold higher, respectively, in islets cultured for 24 h in 11.1 mM glucose compared with those incubated in the presence of 5.5 mM glucose. Therefore, the previously observed increase in GLUT2 MRNA levels in the islets of rats made hyperglycemic by chronic infusion of glucose can be mimicked in vitro, implying that glucose regulates GLUT2 MRNA expression. Less