Reinvestigation of hyperglycemic response to glucagon and the effect of glucagon on blood cholesterol and triglyceride concentrations. (2) Changes in liver disease (author's transl)

Abstract

Early preparations of glucagon were contaminated by considerable amounts of insulin and other impurities. This led us to the reinvestigation of hyperglycemic response using a recent glucagon preparation which contained very little insulin (5 mu/mg). Since little is known about the influence of glucagon on the cholesterol and triglyceride metabolism and also because the carbohydrate metabolism is closely related to the lipid metabolism, blood concentrations of cholesterol and triglyceride were determined after glucagon administration. In the previous report, hyperglycemic response to glucagon in diabetics was found to be positively correlated with fasting blood glucose, which differed entirely from earlier reported results. Glucagon induced a statistically significant decrease in triglyceride concentration, but no change in cholesterol concentration both in normal and diabetic.In the present study, 34 cases with liver disease including 18 cases with acute hepatitis, 7 cases with chronic hepatitis and 9 cases with cirrhosis of the liver were the subjects investigated. Glucagon, 1 mg dissolved in 20 ml of physiological saline, was injected intra venously and blood specimens were analyzed before and 15, 30, 45, 60, 90 and 120 minutes after administration.(1) The mean maximum increment of blood glucose in acute hepatitis (14.4±2.3mg/dl, Mean ±SEM) and liver cirrhosis (22.9 ±5.1 mg/dl) were significantly lower compared to the normal controls (44.6 ±4.3mg/dl). The increment in chronic hepatitis (29.7 ±6.3mg/dl) tended to decrease. In acute hepatitis, maximum glucose response to glucagon correlated inversely with the degree of jaundice. The peak time of blood glucose was more delayed than in normals. In chronic hepatitis and liver cirrhosis, the return of blood glucose to basal levels was also more delayed than in normals.Insulin secretion after glucagon injection was almost abolished in acute hepatitis. On the contrary, in chronic liver disease, especially in cirrhosis of the liver, EIRI was calculated to be higher than in normals. Furthermore, significant improvement of both hyperglycemic and insulin response to glucagon were obtained in acute hepatitis after the treatment. (2) Blood triglyceride concentrations after glucagon were shown to be not constant in individual cases. The mean concentrations of triglyceride in acute and chronic hepatitis during the experiment showed a very slight and transient decrease and in liver cirrhosis, a little increase at the end of the experiment. No change was also observed in blood cholesterol concentrations in the cases studied. These results clearly indicate a decrease of liver glycogen storage in liver disease and suggest that a glucagon tolerance test in liver disease might be a promising method for evaluating both glucose tolerance and liver function as one of the auxiliary tests.