Effect of Endotoxin Administration on Heart Glycolytic Enzyme Activities in Normal and Diabetic Dogs 1

Abstract

Abstract

The effects of Escherichia coli endotoxin administration on the activities of key glycolytic enzymes in normal and alloxan-diabetic dog hearts were studied and the results were correlated with changes in plasma glucose concentrations. Normal dogs had a fasting plasma glucose concentration of 100 mg%, which was increased to 130 mg% 1 hr posten-dotoxin, then followed by a progressive decrease at 2 hr and thereafter to hypoglycemic levels (68 mg% at 4 hr). Diabetic dogs had a fasting plasma glucose concentration of 360 mg%, which was decreased to and maintained at 250 mg% at 2 and 4 hr following endotoxin injection. Hexokinase activity was not significantly different between the normal and diabetic dogs (P = 0.09). After endotoxin injection hexokinase activity tended to increase at 2 to 4 hr (P = 0.056) but it did not respond differently between the two groups, normal versus diabetic (P = 0.29). Phosphofructokinase activity was not different between normal and diabetic dogs (P = 0.49). After endotoxin injection phosphofructokinase activity was depressed at 2 hr but returned nearly to the control value at 4 hr (P = 0.48); there was no indication that this response with time differed between normal and diabetic dogs (P = 0.64). In normal dogs, pyruvate kinase activity was increased by 152.8% at 2 hr but then returned to the control value 4 hr after endotoxin injection. In alloxan diabetes, pyruvate kinase activity was increased by 216.8% at 2 hr and then further increased to 425.4% at 4 hr following endotoxin injection. Postendotoxic pyruvate kinase activity in diabetic dogs was significantly higher than that in normal dogs (P < 0.01) and also the change in pyruvate kinase activity with time differed significantly between the two groups (P < 0.01). Since the transport of glucose across myocardial cells has been found to be unaltered by endotoxin, it is concluded that the increase in pyruvate kinase activity is responsible at least in part for the augmented glycolysis of the myocardium during endotoxic shock.