DIFFERENCES IN THE BLOOD GLUCOSE RESPONSE OF MICE TO ALLOXAN AND ALLOXAN-INHIBITING COMPOUNDS

Abstract

ABSTRACT A typical triphasic blood glucose response (response A) is seen in fed and starved mice treated with alloxan alone, whereas a marked initial hyperglycaemia (to which alloxan probably has not contributed) and an abolished second hyperglycaemia (response B) are found in starved mice given D-glucose, D-fructose, D-mannose, and sodium lactate, and in fed mice treated with p-hydroxymercurigenzoate (PMB), D-mannoheptulose (MH) or diphenylhydantoin (DPH) before alloxan injection. An abolished initial hyperglycaemia, but a preserved "second" hyperglycaemia (response C), is observed in starved mice given PMB, MH or DPH before alloxan, indicating that an initial hyperglycaemia is not a prerequisite for B-cell damage and development of alloxan diabetes. Fed and starved mice pre-treated with NaHCO3, acetazolamide (AZM), L-leucine or tolbutamide exhibit neither any initial nor any second hyperglycaemia (response D) following alloxan injection. The findings suggest that the inhibition of alloxan toxicity caused by pre-treatment with D- glucose, D-fructose, D-mannose, PMB, MH or DPH, and to some extent also sodium lactate, is dependent upon development of hyperglycaemia which may affect the B-cells secondarily and make them insensitive to alloxan, whereas these compounds are not antagonistic to alloxan in the absence of hyperglycaemia, e.g. when PMB, MH or DPH are given to starved mice. NaHCO3, AZM, L-leucine and tolbutamide seem to antagonize alloxan by other mechanism(s), probably through a direct action upon the B-cells.