Amino acid and alpha-keto acid-induced hyperinsulinism in the leucine-sensitive type of infantile and childhood hypoglycemia

Abstract

Summary 1.Studies on 2 patients with leucine-induced “idiopathic” hypoglycemia showed that l-isoleucine also caused a striking fall in the concentration of blood glucose. d-leucine, l-valine, l-alanine, dl-threonine, and l-glycine did not have a significant effect. 2.The α-keto acid analogue of leucine, α-ketoisocaproic acid, induced hypoglycemia when injected intravenously but not its metabolite isovaleric acid. Its action was less effective orally. Pyruvic acid and α-ketoisovaleric acid failed to elicit a similar response. 3.No evidence of a defect in amino acid or α-keto acid metabolism was found, nor of a direct effect of leucine on glycolysis in whole blood. 4.It was shown that leucine caused increased peripheral utilization of glucose, suggesting an insulin-like action. Direct determinations of plasma insulin indicated a sharp rise in circulating insulin following the administration of leucine. 5.It is concluded that l-leucine, l-isoleucine, and their keto acid analogues induce an increase in the concentration of plasma insulin irrespective of the blood glucose level, an effect which may be attributed to their direct action on the mechanism of insulin secretion. Summary 1.Studies on 2 patients with leucine-induced “idiopathic” hypoglycemia showed that l-isoleucine also caused a striking fall in the concentration of blood glucose. d-leucine, l-valine, l-alanine, dl-threonine, and l-glycine did not have a significant effect. 2.The α-keto acid analogue of leucine, α-ketoisocaproic acid, induced hypoglycemia when injected intravenously but not its metabolite isovaleric acid. Its action was less effective orally. Pyruvic acid and α-ketoisovaleric acid failed to elicit a similar response. 3.No evidence of a defect in amino acid or α-keto acid metabolism was found, nor of a direct effect of leucine on glycolysis in whole blood. 4.It was shown that leucine caused increased peripheral utilization of glucose, suggesting an insulin-like action. Direct determinations of plasma insulin indicated a sharp rise in circulating insulin following the administration of leucine. 5.It is concluded that l-leucine, l-isoleucine, and their keto acid analogues induce an increase in the concentration of plasma insulin irrespective of the blood glucose level, an effect which may be attributed to their direct action on the mechanism of insulin secretion.