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 metabolism, but; the effects on protein metabo lism are unclear. Because amino acids are an important substrate for glucon eogenesis and a fuel alternative to glucose for oxidation, we evaluated whe ther hypoglycemia antagonizes the hypoaminoacidemic and the antiproteolytic effects of insulin and changes the de novo synthesis of glutamine, a gluco neogenic amino acid. To this purpose, in 7 healthy subjects, we performed 2 studies, 3.5 h each, at similar insulin but different glucose concentratio ns (i.e., 4.9 +/- 0.1 mmol/l [euglycemic clamp] or 2.9 +/- 0.2 mmol/l [hypo glycemic clamp]). As expected, hypoglycemia antagonized the insulin suppres sion of glucose production achieved in euglycemia (from 21 +/- 15 to 116 +/ - 12% of basal, P < 0.001), the stimulation of glucose uptake (from 207 +/- 28 to 103 +/- 7% of basal, P < 0.01) and the suppression of circulating fr ee fatty acids (from 30 +/- 5 to 80 +/- 170m of basal, P < 0.001). In contr ast, hypoglycemia increased the insulin suppression of circulating leucine (from 63 +/- 1 to 46 +/- 2% of basal, P < 0.001) and phenylalanine (from 79 +/- 3 to 64 +/- 39g of basal, P < 0.001) concentrations. Hypoglycemia did not change the insulin suppression of proteolysis (from 79 +/- 2 to 82 +/- 4% of basal, P < 0.001), However, hypoglycemia doubled the insulin suppress ion of the glutamine concentrations (from 84 +/- 3 to 63 +/- 3% of basal, P < 0.01) in the absence of significant changes in the glutamine rate of app earance, but it also caused an imbalance between glutamine uptake and relea se, This study demonstrates that successful counterregulation does not affe ct; proteolysis. Moreover, it does not increase the availability of circula ting amino acids by de novo synthesis. In contrast, despite the lower conce ntration of circulating amino acids, hypoglycemia increases the uptake of g lutamine that can be used for gluconeogenesis and as a fuel alternative to glucose.