TY - JOUR
T1 - Protein dynamics in whole body and in splanchnic and leg tissues in type I diabetic patients
AU - Nair, K. Sreekumaran
AU - Ford, G. Charles
AU - Ekberg, Karin
AU - Fernqvist-Forbes, Eva
AU - Wahren, John
PY - 1995/6
Y1 - 1995/6
N2 - To elucidate the mechanism or insulin's anticatabolic effect in humans, protein dynamics were evaluated in the whole-body, splanchnic, and leg tissues in six C-peptide-negative type I diabetic male patients in the insulin-deprived and insulin-treated states using two separate amino acid models (leucine and phenylalanine). L-(1-13C, 15N) leucine, L-(ring2H5) phenylalanine, and L- (ring- 2H2) tyrosine were infused intravenously, and isotopic enrichments or [1-13C,15N]-leucine, (13C)leucine, (13C)ketoisocaproate, (2H5)phenylalanine, [2H4] tyrosine, (2H2)tyrosine, and 13CO2 were measured in arterial, hepatic vein, and femoral vein samples. Whole-body leucine flux, phenylalanine flux, and tyrosine flux were decreased (< 0.01) by insulin treatment, indicating an inhibition of protein breakdown. Moreover, insulin decreased (< 0.05) the rates of leucine oxidation and leucine transamination (P < 0.01), but the percent rate of ketoisocaproate oxidation was increased by insulin (P < 0.01). Insulin also reduced (< 0.01) whole-body protein synthesis estimated from both the leucine model (nonoxidative leucine disposal) and the phenylalanine model (disposal of phenylalanine not accounted by its conversion to tyrosine). Regional studies demonstrated that changes in whole body protein breakdown are accounted for by changes in both splanchnic and leg tissues. The changes in whole-body protein synthesis were not associated with changes in skeletal muscle (leg) protein synthesis but could be accounted for by the splanchnic region. We conclude that though insulin decreases whole-body protein breakdown in patients with type I diabetes by inhibition of protein breakdown in splanchnic and leg tissues, it selectively decreases protein synthesis in splanchnic tissues, which accounted for the observed decrease in whole-body protein synthesis. Insulin also augmented anabolism by decreasing leucine transamination.
AB - To elucidate the mechanism or insulin's anticatabolic effect in humans, protein dynamics were evaluated in the whole-body, splanchnic, and leg tissues in six C-peptide-negative type I diabetic male patients in the insulin-deprived and insulin-treated states using two separate amino acid models (leucine and phenylalanine). L-(1-13C, 15N) leucine, L-(ring2H5) phenylalanine, and L- (ring- 2H2) tyrosine were infused intravenously, and isotopic enrichments or [1-13C,15N]-leucine, (13C)leucine, (13C)ketoisocaproate, (2H5)phenylalanine, [2H4] tyrosine, (2H2)tyrosine, and 13CO2 were measured in arterial, hepatic vein, and femoral vein samples. Whole-body leucine flux, phenylalanine flux, and tyrosine flux were decreased (< 0.01) by insulin treatment, indicating an inhibition of protein breakdown. Moreover, insulin decreased (< 0.05) the rates of leucine oxidation and leucine transamination (P < 0.01), but the percent rate of ketoisocaproate oxidation was increased by insulin (P < 0.01). Insulin also reduced (< 0.01) whole-body protein synthesis estimated from both the leucine model (nonoxidative leucine disposal) and the phenylalanine model (disposal of phenylalanine not accounted by its conversion to tyrosine). Regional studies demonstrated that changes in whole body protein breakdown are accounted for by changes in both splanchnic and leg tissues. The changes in whole-body protein synthesis were not associated with changes in skeletal muscle (leg) protein synthesis but could be accounted for by the splanchnic region. We conclude that though insulin decreases whole-body protein breakdown in patients with type I diabetes by inhibition of protein breakdown in splanchnic and leg tissues, it selectively decreases protein synthesis in splanchnic tissues, which accounted for the observed decrease in whole-body protein synthesis. Insulin also augmented anabolism by decreasing leucine transamination.
KW - muscle
KW - protein breakdown
KW - protein synthesis
KW - splanchnic
KW - type I diabetes
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U2 - 10.1172/JCI118000
DO - 10.1172/JCI118000
M3 - Article
C2 - 7769135
AN - SCOPUS:0029073033
SN - 0021-9738
VL - 95
SP - 2926
EP - 2937
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 6
ER -