EFFECT OF GLUCAGON ON THE XYLITOL-INDUCED INCREASE IN THE PLASMA-CONCENTRATION AND URINARY-EXCRETION OF PURINE-BASES

To investigate whether glucagon affects the xylitol-induced increase i n the production of purine bases (hypoxanthine, xanthine, and uric aci d), the present study was performed with five healthy subjects. intrav enous administration of 300 mt 10% xylitol increased the plasma concen tration and urinary excretion of purine bases, erythrocyte concentrati ons of adenosine monophosphate (AMP) and adenosine diphosphate (ADP), end blood concentrations of glyceraldehyde-3-phosphate (GABP) + dihydr oxyacetone phosphate (DHAP), fructose-1,6-bisphosphate (FBP), and tact ic acid; it decreased the blood concentration of pyruvic acid and the plasma concentration and urinary excretion of inorganic phosphate. How ever, intravenous administration of 1 mg glucagon together with xylito l reduced the xylitol-induced changes in oxypurines, pyruvic acid, GAB P + DHAP, and FBP, whereas it promoted the xylitol-induced increase in the urinary excretion of total purine bases and did not affect the xy litol-induced increase in the plasma concentration of total purine bas es. In addition, in vitro study demonstrated that sodium pyruvate prev ented the xylitol-induced degradation of adenine nucleotides in erythr ocytes. These results suggested that gluconeogenesis due to glucagon i ncreased the production of pyruvic acid, accelerated the conversion of NADH to NAD. and thereby prevented both the xylitol-induced degradati on of adenine nucleotides in organs similar to erythrocytes and the in hibition of xanthine dehydrogenase in the liver and small intestine, r esulting in decreases in the plasma concentration and urinary excretio n of oxypurines. However, it was also suggested that in the liver stor ing glycogen, glucagon-induced glycogenolysis accumulated sugar phosph ates, resulting in purine degradation, since the xylitol-induced incre ase in the NADH/NAD ratio partially blocked glycolysis at the level of GABP dehydrogenase. Therefore, administration of glucagon together wi th xylitol may synergistically increase purine degradation more than x ylitol alone, despite decreases in the plasma concentration and urinar y excretion of oxypurines. Copyright (C) 1996 by W.B. Saunders Company