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

R. Buckspan, B. Hoxworth, E. Cersosimo, J. Devlin, E. Horton, N. Abumrad

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

The present study was designed to examine the glucose-sparing effect of leucine and its keto acid α-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 μmol·kg-1·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·kg-1·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 μmol·kg-1·min-1 for 3 h. The amount of exogenous glucose required to maintain euglucemia (M, mg·kg-1·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·kg-1·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·kg-1·min-1, P = NS). On the other hand, the combination of KIC and insulin resulted in a near 20% decrease in both forearm glucose uptake and an increase in the amount of lactate release across the forearm (P < 0.05, both). Our data indicate that KIC is more potent than its parent amino acid, leucine, in sparing glucose utilization in humans. The exact mechanism of this effect is not clear but is most likely related to both an inhibition of glycogen deposition by skeletal muscle and inhibition of pyruvate dehydrogenase enzyme complex by the same tissues.

Original languageEnglish (US)
Pages (from-to)14/6
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume251
Issue number6
StatePublished - 1986
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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