Effect of hypoglycemia on amino acid and protein metabolism in healthy humans

In response to hypoglycemia, healthy individuals rapidly antagonize insulin action on glucose and lipid metabo-lism, but the effects on protein metabolism are unclear. Because amino acids are an important substrate for gluconeogenesis and a fuel alternative to glucose for oxidation, we evaluated whether hypoglycemia antago-nizes the hypoaminoacidemic and the antiproteolytic effects of insulin and changes the de novo synthesis of glutamine, a gluconeogenic amino acid. To this purpose, in 7 healthy subjects, we performed 2 studies, 3.5 h each, at similar insulin but different glucose concen-trations (i.e., 4.9 ± 0.1 mmol/l [euglycemic clamp] or 2.9 ± 0.2 mmol/l [hypoglycemic clamp]). As expected, hypoglycemia antagonized the insulin suppression of glucose production achieved in euglycemia (from 21