Alloxan diabetogenicity: determinants of potentiation, protection and B-cell selectivity.
Compounds with a reported in vivo and in vitro effect on the diabetogenicity of alloxan were studied with regard to the uptake of calcium in mouse islet mitochondria, with the aim of obtaining information on the susceptibility and selectivity of alloxan toxicity. A strong correlation was found between the uptake of calcium in mouse islet mitochondria, which is believed to be associated with the activation of oxidative enzymes involved in energy production and secretion of insulin, and the protection afforded by the injection of D-glucose, D-mannose, L-leucine and glucagon, and by the in vitro administration of cyclic AMP, L-glutamine and L-leucine. The effect of D-glucose was abolished by D-mannoheptulose. A correlation was also seen between reduced mitochondrial uptake of calcium and the potentiation of alloxan cytotoxicity afforded by 1.25-dihydroxycholecalciferol, methylene blue and menadione. The observations suggest an association between functional activity and alloxan cytotoxicity. The selectivity of the cytotoxic action of alloxan is believed to be dependent on a reduced mitochondrial uptake of calcium and an associated reduction of the energy production at low functional activity in the B-cells (e.g. in starvation which is well-known to potentiate the alloxan effect).
Boquist
L
L
Institute of Pathology, University of Umeå, Sweden.
D000496:Alloxan / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005260:Female; D005973:Glutamine / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007930:Leucine / Q000494:pharmacology; D008297:Male; D051379:Mice; D008820:Mice, Obese; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D014812:Vitamin K / Q000494:pharmacology
D001786:Blood Glucose; D005973:Glutamine; D014812:Vitamin K; D000496:Alloxan; D000242:Cyclic AMP; D002117:Calcitriol; D007930:Leucine; D002118:Calcium