TY - JOUR
T1 - Arterial KIC as marker of liver and muscle intracellular leucine pools in healthy and type 1 diabetic humans
AU - Barazzoni, R.
AU - Meek, S. E.
AU - Ekberg, K.
AU - Wahren, J.
AU - Nair, K. S.
PY - 1999/8
Y1 - 1999/8
N2 - In human protein turnover studies with isotopically labeled leucine (Leu) as a tracer, plasma ketoisocaproate (KIC) enrichment is extensively used as a surrogate measure of intracellular leucine enrichment. To test how accurately arterial ketoisocaproate (A-KIC) represents leucine isotopic enrichment in the hepatic (HV) and femoral veins (FV), which drain liver and muscle beds, we measured Leu and KIC enrichments in samples collected from HV, FV, and femoral artery (A) in 24 control and 6 type I diabetic subjects after a primed, continuous infusion of L-[1-13C,15N]-Leu. Studies were performed during insulin deprivation or insulin replacement in the diabetic group, whereas the effect of normal saline or three different doses of insulin infusion (0.25, 0.50, and 1 mU · kg-1 · min-1) were assessed in healthy controls. The ratios of baseline isotopic enrichments of A-KIC to HV Leu and FV Leu were 0.93 ± 0.01 and 0.94 ± 0.02, respectively, in normal subjects and 1.07 ± 0.04 and 1.05 ± 0.03, respectively, in diabetic subjects (P < 0.01, diabetic vs. normal subjects). Insulin did not change A- KIC-to-HV Leu ratios in either group, but the A-KIC-to-FV Leu ratio decreased during insulin infusion in normal subjects (P < 0.05). In conclusion, A-KIC represents a reliable surrogate measure of HV Leu enrichment at different levels of circulating insulin in humans. The present data support the use of A-KIC as a surrogate precursor pool for hepatic protein synthesis.
AB - In human protein turnover studies with isotopically labeled leucine (Leu) as a tracer, plasma ketoisocaproate (KIC) enrichment is extensively used as a surrogate measure of intracellular leucine enrichment. To test how accurately arterial ketoisocaproate (A-KIC) represents leucine isotopic enrichment in the hepatic (HV) and femoral veins (FV), which drain liver and muscle beds, we measured Leu and KIC enrichments in samples collected from HV, FV, and femoral artery (A) in 24 control and 6 type I diabetic subjects after a primed, continuous infusion of L-[1-13C,15N]-Leu. Studies were performed during insulin deprivation or insulin replacement in the diabetic group, whereas the effect of normal saline or three different doses of insulin infusion (0.25, 0.50, and 1 mU · kg-1 · min-1) were assessed in healthy controls. The ratios of baseline isotopic enrichments of A-KIC to HV Leu and FV Leu were 0.93 ± 0.01 and 0.94 ± 0.02, respectively, in normal subjects and 1.07 ± 0.04 and 1.05 ± 0.03, respectively, in diabetic subjects (P < 0.01, diabetic vs. normal subjects). Insulin did not change A- KIC-to-HV Leu ratios in either group, but the A-KIC-to-FV Leu ratio decreased during insulin infusion in normal subjects (P < 0.05). In conclusion, A-KIC represents a reliable surrogate measure of HV Leu enrichment at different levels of circulating insulin in humans. The present data support the use of A-KIC as a surrogate precursor pool for hepatic protein synthesis.
KW - Ketoisocaproic acid
KW - Precursor pool
KW - Protein synthesis
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U2 - 10.1152/ajpendo.1999.277.2.e238
DO - 10.1152/ajpendo.1999.277.2.e238
M3 - Article
C2 - 10444418
AN - SCOPUS:0032854224
SN - 0193-1849
VL - 277
SP - E238-E244
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
IS - 2 40-2
ER -