Pancreatic beta cell toxicity by streptozotocin anomers

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Abstract
D-glucose in the pyranose (ring) form exists as two anomers. The α-anomer is more effective than the β-anomer in promoting insulin secretion, suppressing that of glucagon, and protecting β-cells against alloxan toxicity. Streptozotocin (SZ), a beta cell toxin, is composed of a cytotoxk moiety, 1-methyl 1-nitrosourea, attached to carbon-2 of glucose and exists as either of rwo anomers in the pyranose form. In 24-hour-fasted male rats, predominantly α-or predominantly β-SZ was injected intravenously and plasma glucose levels were obtained 48 hours later. The α-anomer produced significantly greater β-cell necrosis at doses of 30, 35, and 40 mg./ kg. body weight. At higher doses, no differences between the α and βanomers were observed. 3-O-Methyl glucose (3-OMG) protected against both SZ anomers; however, the α-SZ remained more toxic. Larger doses of glucose protected against the lower doses of SZ and, under such conditions, the individual glucose anomers appeared equally potent. Finally, mannitol at comparable molar concentrations was ineffective in protecting against the SZ toxkity. This study suggests that streptozotocin's beta cell toxicity is mediated through recognition by the beta cell. In addition, 3-OMG and, to a lesser but significant extent, glucose were shown to protect against the streptozotocin toxkity, whereas mannitol did not.

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