Protein dynamics in whole body and in splanchnic and leg tissues in type I diabetic patients

K Sreekumaran Nair, G. C. Ford, K. Ekberg, E. Fernqvist-Forbes, J. Wahren

Research output: Contribution to journalArticle

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Abstract

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-(ring 2H 5) phenylalanine, and L- (ring- 2H 2) tyrosine were infused intravenously, and isotopic enrichments or [1- 13C, 15N]-leucine, ( 13C)leucine, ( 13C)ketoisocaproate, ( 2H 5)phenylalanine, [ 2H 4] tyrosine, ( 2H 2)tyrosine, and 13CO 2 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.

Original languageEnglish (US)
Pages (from-to)2926-2937
Number of pages12
JournalJournal of Clinical Investigation
Volume95
Issue number6
StatePublished - 1995

Fingerprint

Viscera
Leucine
Leg
Phenylalanine
Insulin
Proteins
Tyrosine
Hepatic Veins
Femoral Vein
Muscle Proteins
C-Peptide
Type 1 Diabetes Mellitus
Skeletal Muscle
Amino Acids

Keywords

  • muscle
  • protein breakdown
  • protein synthesis
  • splanchnic
  • type I diabetes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Nair, K. S., Ford, G. C., Ekberg, K., Fernqvist-Forbes, E., & Wahren, J. (1995). Protein dynamics in whole body and in splanchnic and leg tissues in type I diabetic patients. Journal of Clinical Investigation, 95(6), 2926-2937.

Protein dynamics in whole body and in splanchnic and leg tissues in type I diabetic patients. / Nair, K Sreekumaran; Ford, G. C.; Ekberg, K.; Fernqvist-Forbes, E.; Wahren, J.

In: Journal of Clinical Investigation, Vol. 95, No. 6, 1995, p. 2926-2937.

Research output: Contribution to journalArticle

Nair, KS, Ford, GC, Ekberg, K, Fernqvist-Forbes, E & Wahren, J 1995, 'Protein dynamics in whole body and in splanchnic and leg tissues in type I diabetic patients', Journal of Clinical Investigation, vol. 95, no. 6, pp. 2926-2937.
Nair, K Sreekumaran ; Ford, G. C. ; Ekberg, K. ; Fernqvist-Forbes, E. ; Wahren, J. / Protein dynamics in whole body and in splanchnic and leg tissues in type I diabetic patients. In: Journal of Clinical Investigation. 1995 ; Vol. 95, No. 6. pp. 2926-2937.
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