Effect of Euglycemic Insulin Infusion on Plasma Levels of Branched–Chain Amino Acids in Cirrhosis

Abstract

To test the hypothesis that hyperinsulinism is responsible for reduced branched–chain amino acids in cirrhotics, plasma amino acids were sequentially determined in 8 controls and 8 matched cirrhotics during continuous i.v. insulin infusion. An artificial endocrine pancreas which infused glucose was used to sustain euglycemia. Basal plasma insulin levels were high and branched–chain amino acids were reduced in cirrhotics. Insulin infusion raised insulin levels to 3 to 4 times basal values. During the test, the decline in branched–chain amino acids was markedly higher in controls who had similar steady–state insulin levels. Not only did the level of branched–chain amino acids in controls reach the values seen in cirrhotics after 60 min, but the levels continued to fall at a significantly higher rate throughout the second hour. Glucose consumption and the ratio of glucose infused/steady–state insulin—a measure of tissue sensitivity to insulin—were markedly reduced in cirrhotics and positively correlated with the decline in branched–chain amino acids. In cirrhotics, insulin effects on carbohydrate and branched–chain amino acid metabolism were reduced. Low branched–chain amino acid levels in cirrhotics are not likely to depend only on hyperinsulinism.