Prevention of high- and low-dose STZ-induced diabetes with D-glucose and 5-thio-D-glucose

To induce hyperglycemia in mice by administration of STZ, two experimental protocols that involve different pathogenic pathways are being used. First, the intraperitoneal injection of a single high dose (HD-STZ) exerts direct toxicity on beta-cells, which results in necrosis within 48-72 h and overt permanent hyperglycemia. Second, injections of multiple low doses of STZ (LD-STZ), administered intraperitoneally on 5 consecutive days, induce both beta-cytotoxic effects and STZ-specific T-cell-dependent immune reactions. In LD-STZ models, only a combination of toxic and immunological effects result in gradually increasing hyperglycemia, provided male mice of susceptible strains are being used. In this study, we found that 5-T-G, a glucose analogue that has sulfur for oxygen in the pyranose ring, prevented, in a dose-dependent way, both HD-STZ- and LD-STZ-induced hyperglycemia and that D-G, which was only tested in the LD-STZ system, was also protective, albeit somewhat less so than 5-T-G. This protective effect was achieved by intraperitoneally injecting 5-T-G and D-G, respectively, right before each STZ injection. Protection against hyperglycemia was already achieved with a total of 3 injections of 5-T-G, 1 injection each given before the first 3 of 5 LD-STZ injections. By means of OGTT, it was determined that pretreatment with 5-T-G afforded protection from substantial beta-cell damage in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)