title: The relationship between the physicochemical properties and the biological effects of alloxan and several N-alkyl substituted alloxan derivatives.
abstract: Alloxan causes diabetes in experimental animals through its ability to destroy the insulin-secreting B-cells of the pancreas. Alloxan is hydrophilic and chemically unstable; it is reactive toward thiols, undergoing redox cycling in the presence of glutathione and oxidizing protein-bound thiol groups, as reflected by inhibition of the thiol enzymes, hexokinase and glucokinase. It is apparently also selectively taken up by the GLUT-2 glucose transporter in the pancreatic B-cell membrane. In order to investigate which, if any, of these physicochemical properties are important in the toxic action of alloxan, we have examined seven N-alkyl substituted alloxan derivatives of various diabetogenic activity. Hydrophilicity was identified as a factor essential for diabetogenicity. Stability, rate of redox cycling and reactivity toward thiol groups were not correlated with diabetogenicity. Selective uptake by the GLUT-2 glucose transporter is not a prerequisite for the diabetogenicity of alloxan derivatives.
authors.affiliation: Ruakura Agricultural Research Centre, Hamilton, New Zealand.
authors.forename: R
authors.initials: R
authors.lastname: Munday
authors.forename: K
authors.initials: K
authors.lastname: Ludwig
authors.forename: S
authors.initials: S
authors.lastname: Lenzen
mesh_terms: D000496:Alloxan / Q000031:analogs & derivatives / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003600:Cytosol / Q000201:enzymology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D005941:Glucokinase / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006593:Hexokinase / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000378:metabolism
chemical_list: D013438:Sulfhydryl Compounds; D000496:Alloxan; D006593:Hexokinase; D005941:Glucokinase; D005947:Glucose