Hepatic amino- to urea-N clearance and forearm amino-N exchange during hypoglycemic and euglycemic hyperinsulinemia in normal man

Background/Aims: Hypoglycemia has well-described effects on glucose metabolism, whereas the possible effects on hepatic amino nitrogen conversion in relation to muscle amino nitrogen flux are more uncertain, Methods: We studied six healthy young male subjects three times, i.e. for 6 h in the basal state, during a 6-h euglycemic hyperinsulinemic (1.5 mU/kg/min) clamp and during a 6-h hypoglycemic (plasma glucose below 2.8 mmol/l) clamp, Alanine (2 mmol/kg body weight/h) was infused for 3 h to describe the relationship between blood amino nitrogen concentrations and hepatic ureagenesis estimated from urea urine excretion and accumulation in body water. The slope of this relationship is denoted functional hepatic nitrogen clearance (FHNC) and quantifies substrate-independent alterations in hepatic amino nitrogen degradation. In parallel, amino nitrogen balances across muscles were estimated by the forearm flux method, Results: Euglycemia decreased circulating glucagon values (100+/-25 ng/l vs. 160+/-30 ng/l), whereas hypoglycemia doubled glucagon (350+/-45 ng/l, p<0.05). Hepatic nitrogen clearance (FHNC) decreased during hyperinsulinemic euglycemia (19.5+/-3.4 l/h vs. 30.6+/-5.7 l/h, p<0.01), whereas forearm net uptake of amino nitrogen increased (130+/-40 nmol/100 mix min vs, control: -10+/-4 nmo1/100 ml x min), During hypoglycemia there was a 3-fold increase in hepatic nitrogen clearance up to 83.0 +/- 16.8 l/h (p<0.01) and increased release of amino nitrogen from the forearm (-100+/-30 nmol/100 ml x min, p<0.01), Conclusion: Hypoglycemia in man induces a marked increase in hepatic amino- to urea-N clearance, This catabolic response to hypoglycemia in the liver may be of primary importance for muscle amino acid release, Our data are compatible with the notion that liver and muscle together are responsible for catabolism during hypoglycemia, and that glucagon may be the primary mediator via its effect on liver metabolism.