Pancreatic B-cell sensitivity to alloxan in vivo. A study of antagonizing compounds, serum inorganic phosphate and acid-base balance.

Serum glucose, inorganic phosphate, acid-base balance and islet morphology were studied in mice subjected to different kinds of treatment before alloxan administration. In preceding studies, pretreatment with D-glucose, D-mannose, D-fructose, sodium lactate and NaHCO3, but not with D-galactose, was found to protect against alloxan toxicity. In this study alloxan antagonism was found by pre-treatment with L-leucine, but not with L-arginine or NaH2PO4. Blood analyses, carried out 10 minutes after injection of the test compounds, disclosed that the serum inorganic phosphate concentration was decreased in mice given D-glucose, D-mannose, D-fructose, sodium lactate, NaHCO3, L-leucine, and L-arginine, but was not affected in those treated with D-galactose, and was increased in those receiving NaH2PO4. With the exception of L-arginine, blood pH was increased in the groups which exhibited decreased serum inorganic phosphate concentration; pH was not affected in mice treated with D-galactose, L-arginine and NaH2PO4. Alterations in inorganic phosphate and hydrogen ion concentration may affect the B-cell sensitivity to alloxan ("Pi-pH hypothesis").