Effect of ammonia on glucagon secretion from the perfused pancreas of cirrhotic rats

Summary Effects of ammonia on glucagon and insulin secretion from the perfused pancreas of cirrhotic rats were investigated to clarify the occurring mechanism of hypersecretion of pancreatic glucagon in liver cirrhotics. The results were as follows: (a) During ammonia loading, insulin secretion was inhibited in a dose-related manner, whereas glucagon secretion was gradually increased at high concentrations of ammonia (2 mM) in control rats; this tendency was augmented in the presence of α-ketoglutarate in cirrhotic rats. (b) On cessation of ammonia loading, a transient but definite increase in glucagon and insulin secretion was observed. (c) Basal plasma glucagon and ammonia levels as well as basal glucagon secretion from the perfused pancreas of cirrhotic rats were significantly higher than in control rats. Basal insulin secretion from the perfused pancreas of cirrhotic rats was not different in spite of high levels of plasma insulin. (d) Glucagon secretory response to glucose and arginine from the perfused pancreas of cirrhotic rats was higher than in the control pancreas, whereas insulin secretion was lower. (e) In these cirrhotic rats, an increase in the number of islet cells, particularly A cells, was observed. These data suggested that hypersecretion of pancreatic glucagon which was responsible for hyperglucagonemia in cirrhotic rats might be attributed to high levels of ammonia and α-ketoglutarate in blood as well as to the fluctuation of abnormal ammonia concentration in blood and to the hypertrophy of islets, particularly of the A cell group due to hypersecretion.