REGULATION OF SKELETAL MUSCLE METABOLISM

Project: Research project

Description

An understanding of the regulation of protein metabolism in skeletal
muscle is required for the development of rational approaches to the
treatment of diabetes mellitus and other disease states that affect
nutrient homeostasis. Toward this end, the overall goal of this project
is to gain a better understanding of the mechanisms by which hormones and
nutrients regulate the pathway of protein synthesis in skeletal muscle.
The specific focus of the project continues to be on translational
control, particularly the regulation of initiation of protein synthesis.
In the next grant period, special attention is to be given to the
mechanism of action of insulin on specific initiation factors,
particularly eIF-2 and eIF-2B. Furthermore, the regulatory role of amino
acids is to be investigated because of the recent demonstration of their
importance in controlling protein synthesis in skeletal muscle in humans.
Additionally, the project is to be extended from skeletal to cardiac
muscle so as to better contrast the variations in translational control
manifested by muscles composed of different fiber types. The specific
aims of the project are: (1) to develop monospecific antibodies and cDNA
clones to individual subunits of initiation factors that are found to be
important in the regulation of protein synthesis in muscle; (2) to
investigate protein and mRNA expression as well as structure/function
relationships of specific initation factors in muscle using monospecific
antibodies and cDNA clones; (3) to investigate the mechanism by which
insulin stimulates initiation of protein synthesis and causes an
enhancement of eIF-2B activity in muscle; (4) to identify in skeletal
muscle the specific initiation factor(s) involved in regulation of
initiation of protein synthesis by amino acids and hormones other than
insulin; and (5) to identify in cardiac muscle the specific initiation
factor(s) involved in the regulation of initiation of protein synthesis
by fatty acids and other oxidizable noncarbohydrate substrates. Overall
, the studies described in this proposal should help to identify
mechanisms by which hormones and nutrients regulate protein synthesis in
skeletal and cardiac muscle. They should also provide new insights into
the biochemical and molecular mechanisms involved in the initiation of
protein synthesis.
StatusActive
Effective start/end date9/1/774/30/22

Funding

  • National Institutes of Health: $383,375.00
  • National Institutes of Health: $383,204.00

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Skeletal Muscle
Proteasome Endopeptidase Complex
Proteins
Leucine
Phosphorylation
Atrophic Muscular Disorders
Sedentary Lifestyle
Muscles
Bed Rest
Muscle Proteins
Protein Biosynthesis
Immobilization
Suspensions
Extremities
Cell Culture Techniques
Technology
Amino Acids
Food
mechanistic target of rapamycin complex 1
Research