Furosemide-induced hyperglycaemia: the implication of glycolytic kinases

Hyperglycaemia is a well known adverse effect of therapy with diuretics. In adipose tissue, hydrochlorothiazide and furosemide inhibit the rate of glucose transport. In skeletal muscle, furosemide decreases the rate of glucose phosphorylation and glycolysis. However, whether furosemide has any direct effect on the activities of any of the glycolytic enzymes is not known. In the present study, the effects of furosemide on the activities of the hexokinase, phosphofructokinase and pyruvate kinase were examined. Pieces of skeletal muscle (quadriceps) and liver were obtained from 10 non-diabetic subjects during surgery. Tissues were homogenized and the activities of the enzymes were measured in the 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 lower than that required to inhibit the activity of this enzyme in the liver or to inhibit the activities of hexokinase and pyruvate kinase in both muscle and liver. These direct effects of furosemide may contribute to the decrease in glucose utilisation following therapy with this and similar agents in man.