Project: Research project

Project Details


Even though hyperglucagonemia coexists with insulin deficiency in
a variety of clinical conditions with accelerated urinary nitrogen
excretion, and hypoaminoacidemia is characteristic of patients
with glucagonoma, glucagon's effect on protein synthesis and
degradation remains incompletely defined. The major objective
of the present proposal is to gain better understanding on the
effect of glucagon on protein synthesis and degradation in man,
and to define its action on protein balance in relation to insulin.
Our preliminary studies indicate that insulin causes positive
protein balance in the postabsorptive state by inhibiting
proteolysis and not by stimulating protein synthesis. The present
study will measure the effect of insulin on protein synthesis in the
postabsorptive man and also in subjects infused with a mixture of
essential amino acids to determine the role of plasma amino acid
concentration of insulin's protein synthetic action. Protein
synthesis and proteolysis across leg or foream will be estimated
by measuring the concentration and isotopic abundance of
tyrosine in the arterial and venous plasma together with blood
flow across leg or forearm during a continuous infusion of L-(ring
2H4) tyrosine. Whole body leucine flux will be determined from
plasma (13C)KIC abundance at plateau, and fractional mixed
muscle protein synthesis (FMPS) will be determined from the
increment in (13C) leucine in mixed muscle protein obtained by
serial muscle biopsies during a continuous infusion of L-(1-13C)
leucine. Experiments will be performed in normal volunteers with
infusions of somatostatin and different concentrations of insulin
and glucagon to clearly define the effects of these hormones on
protein synthesis and degradation. The effect of intra-arterial
infusion of glucagon and insulin will be studied to determine
whether an increase in the local concentrations of these hormones
in forearm without any systemic changes affects protein turnover.
Studies will also be done in diabetic patients to test the effect of
insulin treatment and somatostatin infusion on FMPS. Results of
protein synthesis estimated from different techniques will be
compared to check the validity of the conclusions. These
investigations will provide insight into the control of protein
turnover in vivo and the cause of protein catabolism in diabetes
and other catabolic conditions.
Effective start/end date3/1/885/31/89


  • National Institutes of Health
  • National Institutes of Health


  • Medicine(all)


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