GLUT4 AND CARDIAC METABOLISM AND PHYSIOLOGY

Project: Research project

Project Details

Description

DESCRIPTION (adapted from the applicant's abstract): The applicant states
that the expression of GLUT4, the insulin responsive glucose transporter,
found specifically in the heart, skeletal muscle, and adipose tissue, has
been shown to be down regulated in metabolically altered states such as
diabetes and obesity. According to the applicant, GLUT4 null mice
(genetically altered mice which do not make GLUT4) exhibit modified glucose
and fat metabolism, and exhibit significant cardiac hypertrophy independent
of increased arterial blood pressure. The precise mechanisms controlling
the development of this hypertrophy are not well understood. The GLUT4 null
mice and GLUT4 null mice complemented with a transgene specifically
engineered to express GLUT4 in the heart only (HO mice) will be used in in
vivo and in vitro experiments to study the consequences of altered substrate
availability on cardiac structure and function. Experiments employing these
mouse models will answer the following questions: 1. What changes occur in
structure and function in the heart of GLUT4 null mice as hypertrophy
develops, and does putting GLUT4 back into the heart of the HO mouse to make
glucose uptake more normal affect the development of this hypertrophy? In
vitro 31P nuclear magnetic resonance (NMR) spectroscopy and in vivo 1H
magnetic resonance imaging (MRI) will be used at various time points to
evaluate bioenergetic status, myocardial morphology (mass, dimensions) and
function (ejection fraction). 2. What is the substrate utilization profile
in the GLUT4 null and HO hearts as compared to control mice, and do
alterations in these profiles affect function? Isolated perfused hearts of
GLUT4 null and HO mice will be used to determine changes in substrate
utilization and function at different time points in the development of
hypertrophy. 3. How does the hypertrophic heart of the GLUT4 null mouse
and the complemented heart of the HO mouse respond to metabolic and
hemodynamic stress? Several methods will be used to assess what effect the
lack of GLUT4 and its consequent effect on cardiac glucose uptake has on the
ability of the GLUT4 null and HO heart to withstand stress conditions.
StatusFinished
Effective start/end date4/1/973/31/98

Funding

  • National Heart, Lung, and Blood Institute

ASJC

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Endocrinology
  • Physiology
  • Pharmacology

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