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-C-13]LEUCINE

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of insulin on skeletal muscle (anterior tibialis) protein synthesis and whole body leucine turnover in eight insulin-withdrawn Type 1 (insulin-dependent) diabetic patients.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. © 1990 Springer-Verlag.