GLUCOSE-TRANSPORTER-2 EXPRESSION - PREVENTION OF STREPTOZOTOCIN-INDUCED REDUCTION IN BETA-CELLS WITH 5-THIO-D-GLUCOSE

The effect of streptozotocin (STZ) on the glucose transporter 2 (GLUT2 ) expression in beta-cells was investigated in vitro and in vivo. By W estern blot analysis, a gradually decreasing GLUT2 expression was foun d in islets prepared from C57BL/6 male mice that bad received multiple low doses of STZ (MD-STZ) for induction of autoimmune diabetes. Reduc tion of GLUT2 expression correlated with the number of STZ injections administered and preceded development of hyperglycemia. When hyperglyc emia had developed, GLUT2 expression was extremely reduced. In vitro, incubation of isolated islets with STZ resulted in a time- and dose-de pendent reduction of beta-cell GLUT2 expression. In vivo, pretreatment of MD-STZ recipients with intraperitoneal injections with 5-thio-D-gl ucose (5-T-G) just before each of the STZ injections prevented MD-STZ- induced beta-cell GLUT2 reduction and hyperglycemia development. In vi tro, preincubation of islet cultures with 5-T-G also prevented STZ-ind uced GLUT2 reduction. Unlike STZ, equimolar concentrations of methylni trosourea (MNU), the aglycone moiety of STZ, failed to alter GLUT2 exp ression in vitro. In conclusion, our data demonstrate that STZ-induced beta-cell GLUT2 reduction was prevented by 5-T-G both in vitro and in vivo in the MD-STZ diabetes model. The noxious effect of STZ on GLUT2 expression is most likely facilitated through its glucose moiety, bec ause MNU lacked to do so. Presumably, in autoimmune MD-STZ diabetes th e GLUT2 glucose transporter might be a key target structure for STZ su btoxicity and diabetogenicity, which converge with subsequent immune r eactions to beta-cell destruction.