Ganda O P, Rossini A A, Like A A
Diabetes. 1976 Jul;25(7):595-603. doi: 10.2337/diab.25.7.595.
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.
四氧嘧啶和链脲佐菌素均可导致大鼠胰岛β细胞坏死。以往研究表明，D-葡萄糖、D-甘露糖以及非代谢类似物3-O-甲基-D-葡萄糖可对四氧嘧啶毒性起到保护作用，而D-甘露庚酮糖可消除这种保护作用。本研究探讨了几种药物（静脉输注）对链脲佐菌素（60mg/kg静脉注射，用于24小时禁食的200g雄性大鼠）所致β细胞毒性作用的影响。通过24小时和48小时后的血浆葡萄糖浓度来确定保护作用，在某些实验中，还通过胰岛的组织学检查来确定。D-葡萄糖和D-甘露糖未提供保护作用。同样，D-半乳糖、D-果糖、α-甲基-D-葡萄糖苷、D-L-甘油醛、D-木糖和D-葡萄糖胺也无作用。然而，在链脲佐菌素给药前立即给予3-O-甲基-D-葡萄糖可逐渐抑制β细胞毒性，每只大鼠给予0.83毫摩尔时可实现完全保护。3-O-甲基-D-葡萄糖的保护作用不受甘露庚酮糖的影响。2-脱氧-D-葡萄糖对四氧嘧啶无作用，但每只大鼠给予2.2毫摩尔时可对链脲佐菌素提供几乎完全的保护。3-O-甲基-D-葡萄糖和2-脱氧-D-葡萄糖的作用具有相加性，且不受葡萄糖的影响。此外，当在链脲佐菌素给药后给予3-O-甲基-D-葡萄糖和2-脱氧-D-葡萄糖时，尽管作用减弱，但仍存在保护作用。这与四氧嘧啶相反，3-O-甲基-D-葡萄糖仅在四氧嘧啶给药前给予时才对其提供保护作用。3-O-甲基-D-葡萄糖是大鼠体内唯一对链脲佐菌素和四氧嘧啶均有保护作用的碳水化合物。然而，这两种致糖尿病化合物的β细胞毒性作用机制之间似乎存在一些细微差异。
