Inability to stimulate skeletal muscle or whole body protein synthesis in Type 1 (insulin-dependent) diabetic patients by insulin-plus-glucose during amino acid infusion: studies of incorporation and turnover of tracer L-[1-13C]leucine
- 1 January 1990
- journal article
- research article
- Published by Springer Nature in Diabetologia
- Vol. 33 (1) , 43-51
- https://doi.org/10.1007/bf00586460
Abstract
Despite its anabolic effects on protein balance, acute administration of insulin has been reported to have no effect on skeletal muscle or whole body protein synthesis in man. However, insulin also reduces plasma and intramuscular amino acid availability, which may limit protein synthesis. We have therefore measured the acute effects of insulin on skeletal muscle (anterior tibialis) protein synthesis and whole body leucine turnover in eight insulin-withdrawn Type 1 (insulin-dependent) diabetic patients. They were studied initially when insulin deficient, but during infusion of mixed amino acids at a rate sufficient to raise plasma amino acids by 30% i.e. to 4 mmol/l in total; measurements were continued when insulin was infused together with an increased rate of amino acids to maintain insulinopoenic plasma amino acid concentrations. Using13C-α-ketoisocaproate in plasma as an index of the intracellular precursor labelling, incorporation of [1-13C]leucine into skeletal muscle protein was 0.068±0.007%/h during insulin withdrawal and was unaltered during insulin infusion. The value is higher than observed in muscle of healthy man, possibly because of a stimulatory effect of endogenous intramuscular amino acids. Also, calculated on the basis of α-ketoisocaproate labelling, non-oxidised whole body leucine disappearance (i. e. whole body protein synthesis) was 110±4 μmol·kg−1·h−1 during insulin withdrawal; this also was unchanged during insulin infusion. Despite stable or increased plasma concentrations of most amino acids, the intramuscular concentrations of a number of amino acids decreased during insulin infusion. This may have limited any anabolic effect of insulin on protein synthesis. Alternatively, pre-existing high intramuscular amino acids may have maximally stimulated muscle protein synthesis, so that the further elevation was obscured, especially with the tendency to depletion of precursor amino acids.Keywords
This publication has 59 references indexed in Scilit:
- The effect of amino acid infusion on leg protein turnover assessed by L‐[15N]phenylalanine and L‐[1‐13C]leucine exchangeEuropean Journal of Clinical Investigation, 1990
- Isolation of amino acids by preparative gas chromatography for quantification of carboxyl carbon13C enrichment by isotope ratio mass spectrometryJournal of Mass Spectrometry, 1988
- Effect of beta-hydroxybutyrate on whole-body leucine kinetics and fractional mixed skeletal muscle protein synthesis in humans.Journal of Clinical Investigation, 1988
- Factors controlling the disposition of primary nutrientsProceedings of the Nutrition Society, 1988
- Automated measurement of the concentration and13C enrichment of carbon dioxide in breath and blood samples using the finnigan MAT breath gas analysis systemJournal of Mass Spectrometry, 1988
- Effect of insulin on hind-limb and whole-body leucine and protein metabolism in fed and fasted lambsBritish Journal of Nutrition, 1987
- Transport kinetics of amino acids across the resting human leg.Journal of Clinical Investigation, 1987
- Inhibition of muscular amino acid release by lipid infusion in manEuropean Journal of Clinical Investigation, 1987
- Effect of physiologic hyperinsulinemia on skeletal muscle protein synthesis and breakdown in man.Journal of Clinical Investigation, 1987
- Differential effects of hyperinsulinemia and hyperaminoacidemia on leucine-carbon metabolism in vivo. Evidence for distinct mechanisms in regulation of net amino acid deposition.Journal of Clinical Investigation, 1987