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