Studies of Alloxan Toxicity on the Beta Cell

Abstract

The ability of sugars to protect the beta cell from alloxan diabetes is highly stereospecific. The α anomer, which is present in equilibrium in both glucose and 3-O-methyl glucose (3-OMG) at approximately 34 per cent, provides greater protection than the β anomer. The greater protection of the α anomer of glucose is present fifteen seconds between its administration and alloxan, but there is no difference in protection following a thirty-second interval. The nonmetabolized analogue, 3-OMG, provides even greater protection than glucose, and this higher affinity is expressed both by the lower dose necessary to provide protection, as well as by the higher dose of mannoheptulose needed to remove the protection. Mannoheptulose not only removes the protection provided by exogenous glucose but sensitizes the beta cell to the toxic effects of alloxan in the fasting state, probably by inhibiting the protection provided by endogenous glucose. Mannoheptulose is able to remove glucose protection before, with, or after the administration of glucose prior to alloxan injection. Finally, the protective effect of both glucose and 3-OMG is time-related, and the protection not only is due to absolute concentration but also appears to be affected by a changing concentration.