IN VIVO REGULATION OF PROTEIN TURNOVER BY HORMONES

Project: Research project

Project Details

Description

Even though hyperglucagonemia coexists with insulin deficiency in a
variety of clinical conditions with accelerated urinary nitrogen
excretion, and even though 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 of the effect of
glucagon on protein synthesis and degradation in man, and to define its
action on protein balance in relation to insulin. Recent evidence
indicates that insulin causes positive protein balance in the
postabsorptive state by inhibiting proteolysis and not by stimulating
protein synthesis. Contrary to the conventional belief, plasma amino
acids seem to modulate insulin's effect on protein synthesis. Experiments
will be performed in normal volunteers with infusion of somatostatin and
varying concentrations of insulin and glucagon to more clearly define the
effects of these hormones on protein synthesis and degradation. Intra-
arterial infusion of glucagon and insulin will be performed to determine
whether an increase in the local concentrations of these hormones in
forearm without any systemic changes affects protein turnover. We will
also study the effect of insulin and glucagon on peripheral tissue-
protein synthesis in postabsorptive man during the infusion of essential
amino acids. These studies will more clearly define the role of plasma
amino acids on insulin and glucagon's action on protein synthesis.
Studies will also be performed in diabetic patients to determine the
effect of somatostatin infusion on fractional mixed skeletal muscle
protein synthesis rate (FMPS) and leucine oxidation. Protein synthesis and degradation in the peripheral tissues will be
measured from the dilution of [2H5} phenylalanine and phenylalanine
balance across leg or forearm during a continuous infusion of L-[ring
2H5] phenylalanine. Whole body leucine flux will be estimated from plasma
[13 C]KIC abundance at plateau, and FMPS will be estimated from the
increment in [13C] leucine in mixed muscle protein obtained by serial
muscle biopsies during a continuous infusion of L-[1-13C] leucine.
Results of proteins synthesis estimated from various techniques will be
compared to check the validity of the conclusions. these investigations
will provide new insight into the control of protein turnover in vivo and
the cause of protein catabolism in diabetes and other catabolic
conditions. A greater understanding of the mechanism of catabolic state
resulting from these studies is likely to stimulate therapeutic research
in many catabolic conditions.
StatusFinished
Effective start/end date7/1/898/31/16

ASJC

  • Medicine(all)