alpha-Ketoisocaproate is superior to leucine in sparing glucose utilization in humans

The present study was designed to examine the glucose-sparing effect of leucine and its keto acid alpha-ketoisocaproate (KIC) in vivo. Two groups of overnight-fasted normal volunteers were studied. In the first group, eight subjects received an intravenous infusion of leucine and six subjects received KIC (2.3 mumol X kg-1 X min-1) for 3 h; on another occasion, all subjects received saline and acted as their own controls. In the second group, 11 subjects received an infusion of 1 mU X kg-1 X min-1 for 3 h with a variable glucose infusion to maintain euglycemia. On another occasion, five subjects received an additional infusion of leucine and six subjects received KIC each at 2.3 mumol X kg-1 X min-1 for 3 h. The amount of exogenous glucose required to maintain euglycemia (M, mg X kg-1 X min-1) was used as an index of total body glucose utilization. Forearm exchange of leucine, KIC, glucose, and lactate was determined in both groups. Both leucine and KIC infusions alone decreased glucose uptake (42 and 40%) and increased lactate release (37 and 116%, respectively). Hyperinsulinemia (6-fold basal) and euglycemia resulted in a fivefold increase in glucose uptake across the human forearm. The amount of exogenous glucose required to maintain euglycemia averaged 7.4 +/- 0.5 mg X kg-1 X min-1. The combination of leucine and insulin infusions did not alter the stimulated forearm glucose uptake nor did it change M (7.25 +/- 0.6 mg X kg-1 X min-1, P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)