Blood Ammonia Levels in Advanced Cirrhosis during Therapeutic Elevation of the Insulin: Glucagon Ratio

Plasma insulin, glucagon and blood ammonia were measured at frequent intervals in four separate nine-hour studies in five patients with advanced cirrhosis who had consistent basal hyperammonemia while on a diet containing 40 to 60 g of protein. In two of the four studies the diet was supplemented hourly with 20 g of glucose orally. Without supplementation mean blood ammonia rose 20 μg per 100 ml, insulin averaged >50 μU per milliliter, and glucagon averaged >160 pg per milliliter. Mean molar insulin:glucagon ratio rose to a peak of 12.3 but was usually below 5. With glucose supplementation, mean insulin rose to 201 μU per milliliter, glucagon fell below basal values, and the insulin: glucagon ratio rose to a peak of 39.2, significantly above the control at all points. In this hormonal setting, blood ammonia did not rise, but declined slightly, a difference that was significant at all six points of comparison after the first hour of the experiment. The improved protein tolerance could reflect reduced ammonia generation from hepatic ureagenesis and from amino acids secondary to the increased mean molar insulin: glucagon ratio. (N Engl J Med 291:168–171, 1974), THE hormones of the islets of Langerhans are widely accepted as important regulators of the rate of hepatic gluconeogenesis, insulin inhibiting this process.