New diabetogenic streptozocin analogue, 3-O-methyl-2-([(methylnitrosoamino) carbonyl]amino)-D-glucopyranose. Evidence for a glucose recognition site on pancreatic B-cells

Abstract

The nonmetabolizable glucose analogue 3-O-methyl-glucose is known to protect pancreatic B-cells against streptozocin (STZ) when injected with or just before STZ. If 3-O-methyl-glucose and the sugar moiety of STZ compete for a glucose recognition site on B-cells, it seemed likely that 3-O-methyl-2-deoxy-2-( [(methylnitrosoamino)carbonyl]amino)-D-glucopyranose, an analogue of STZ with a 3-O-methyl-glucosyl residue, would cause experimental diabetes. This possibility was tested by synthesis of this analogue (alpha-anomer) and comparison of its diabetogenic activity in Wistar rats with that of STZ. Results showed that the compound was diabetogenic and as potent as STZ. This new analogue is the first of the various STZ derivatives reported to show diabetogenic activity. Its activity supports the idea that 3-O-methyl-glucose and STZ bind competitively with a glucose recognition site on pancreatic B-cells.