The effect of insulin and amino acids on muscle and whole body protein turnover in patients with type 1 diabetes

Deficiency of insulin results in a net loss of lean body mass and wasting of muscle. The defect of protein turnover underlying the loss of skeletal muscle could be a reduction in the rate of protein synthesis, an increase in the rate of protein breakdown or a combination of both. In the present work the abnormalities of protein metabolism occurring during insulin deficiency have been investigated in patients with type 1 diabetes, and the acute effects of insulin replacement, during different conditions of nutrient supply, have been investigated both in patients with type 1 diabetes and in healthy subjectsIncorporation of L-(l-23C)leucine into biopsied skeletal muscle, arteriovenous leg exchange of L-(12N)phenylalanine and of L-(l-23C)leucine, and net release of 3-methylhistidine from leg tissues were used to assess muscle mixed protein synthesis, muscle mixed protein turnover and myofibrillar protein breakdown, respectively. Whole-body protein turnover was assessed by tracer dilution using L-(l-23C)leucine and L-(15N)phenylalanine.Infusion of insulin reduced skeletal muscle mixed protein breakdown, both when plasma amino acids were allowed to fall and when their concentrations were elevated by exogenous amino acid infusion. In the diabetic patients muscle protein synthesis was not increased by insulin infusion alone; infusion of insulin combined with amino acids apparently increased synthesis as assessed by phenylalanine exchange but not when assessed by either leucine exchange or incorporation into muscle. In the healthy subjects there was a faster rate of muscle protein synthesis, assessed by phenylalanine exchange, during combined insulin with amino acid infusion in comparison with the diabetic patients. In healthy subjects infusion of mixed amino acids alone exerted an anabolic effect on muscle protein synthesis with little, if any, alteration in the extent of either mixed or myofibrillar muscle protein breakdown. In comparisons with postabsorptive healthy subjects, abnormalities of muscle protein synthesis and breakdown and of amino acid oxidation in were not identified in type 1 diabetic patients during insulin withdrawal.n the diabetic patients infusion of insulin alone reduced whole-body protein breakdown but also reduced protein synthesis to an equivalent extent; there was no net benefit on protein balance. However, infusion of insulin combined with amino acids reduced protein breakdown and improved net balance with no change in synthesis. In contrast, in the healthy subjects the same doses of insulin combined with amino acids stimulated protein synthesis in addition to reducing protein breakdown. The effects of amino acids alone in healthy subjects was both to stimulate whole-body protein synthesis and to reduce protein breakdown.These investigations suggest that insulin exerts an anabolic action by reducing protein breakdown; insulin is only able to increase protein synthesis during conditions of increased amino acid availability. Muscle protein synthesis was resistant to stimulation by insulin in type 1 diabetic patients