Studies on streptozotocin diabetes

Abstract

Both alloxan and streptozotocin produce beta-cell necrosis in the rat. Previous studies have shown protection against alloxan toxicity by D-glucose, D-mannose, and the nonmetabolized analogue 3-0-methyl-D-glucose and removal of this protective effect by D-mannoheptulose. The effect of several agents (i.v. infusion) against the beta-cell toxic effect of streptozotocin (60 mg./kg. i.v. in 24-hour-fasted 200-gm. male rats) was studied. Protection was determined by plasma glucose concentrations 24 and 48 hours later and, in certain experiments, by histologic examination of the islets. D-glucose and D-mannose provided no protection. Similarly, D-galactose, D-fructose, alpha-methyl-D-glucoside, D-L-glyceraldehyde, D-xylose, and D-glucosamine had no effect. However, 3-0-methyl-D-glucose administered immediately before streptozotocin resulted in progressive inhibition of beta-cell toxicity with complete protection at 0.83 mMoles per rat. The protective effect of 3-0-methyl-D-glucose was not altered by mannoheptulose. 2-Deoxy-D-glucose, which has no effect against alloxan, provided nearly complete protection against streptozotocin at 2.2 mMoles per rat. The effects of 3-0-methyl-D-glucose and 2-deoxy-D-glucose were additive and were not altered by glucose. Furthermore, the 3-0-methyl-D-glucose as well as 2-deoxy-D-glucose protective effects were still present, albeit attenuated, when these agents were given following the administration of streptozotocin. This is in contrast to alloxan, against which 3-0-methyl-D-glucose provides protection only when given before alloxan. 3-0-Methyl-D-glucose is the only carbohydrate protective against both streptozotocin and alloxan in the rat. However, several silent differences seem to exist between the mechanisms of beta-cytotoxic effects of these two diabetogenic compounds.