FUROSEMIDE-INDUCED HYPERGLYCEMIA - THE IMPLICATION OF GLYCOLYTIC KINASES

Hyperglycaemia is a well known adverse effect of therapy with diuretic s. In adipose tissue, hydrochlorothiazide and furosemide inhibit the r ate of glucose transport. In skeletal muscle, furosemide decreases the rate of glucose phosphorylation and glycolysis. However, whether furo semide has any direct effect on the activities of any of the glycolyti c enzymes is not known. In the present study, the effects of furosemid e on the activities of the hexokinase, phosphofructokinase and pyruvat e kinase were examined. Pieces of skeletal muscle (quadriceps) and liv er were obtained from 10 non-diabetic subjects during surgery. Tissues were homogenized and the activities of the enzymes were measured in t he presence or absence of furosemide (0-1.5 mM). Furosemide inhibited the activity of all three key glycolytic enzymes. The concentration of furosemide required to inhibit phosphofructokinase in muscle was lowe r than that required to inhibit the activity of this enzyme in the liv er or to inhibit the activities of hexokinase and pyruvate kinase in b oth muscle and liver. These direct effects of furosemide may contribut e to the decrease in glucose utilisation following therapy with this a nd similar agents in man.