REGULATION OF GLUCOSE TRANSPORTER GENE EXPRESSION

Project: Research project

Project Details

Description

The GLUT4 glucose transporter is the major isoform expressed in muscle and
adipose tissue, the two tissue types primarily responsible for the
maintenance of whole body glucose homeostasis. The GLUT4 isoform plays a
key role in this process by facilitating the uptake of glucose in these
tissues in response to insulin stimulation. Regulation of GLUT4 glucose
transporter functions occurs at multiple levels, several of which are
associated with insulin resistance and diabetes. For example, multiple
studies have documented that GLUT4 expression is decreased in states of
insulin-deficient diabetes and fasting. Further patient studies have
suggested a correlation in adipose tissue expression of GLUT4 with NIDDM.
More recently, both the tissue-specific pattern as well as the
hormonal/metabolic regulation of GLUT4 expression have been shown to occur
at the transcriptional level.

Based upon the central role of the GLUT4 gene in the pathophysiology
associated with diabetes, we have proposed a series of studies to address
the tissue-specific and hormonal/metabolic regulation of this gene. The
basic molecular events involved in GLUT4 gene regulation are clearly
important issues which are necessary for our understanding of adipose and
muscle-specific gene regulation as well as for the control of glucose
homeostasis, metabolism and energy production. We therefore plan to
continue our studies delineating the molecular mechanisms responsible for
the hormonal/metabolic and tissue-specific regulation of the insulin-
responsive GLUT4 gene. This will be accomplished by detailed analysis of
GLUT4 promoter function and identification of cis-DNA regulatory elements
using several complementary approaches. These studies will then allow for
the characterization and isolation of tissue-specific DNA binding factors
responsible for the hormonal/metabolic (insulin-deficient diabetes and
fasting/refeeding states) and tissue-specific (white adipose, brown
adipose, cardiac and skeletal muscle) regulation of this gene.
StatusFinished
Effective start/end date9/1/958/31/96

Funding

  • National Institute of Diabetes and Digestive and Kidney Diseases

ASJC

  • Endocrine and Autonomic Systems
  • Endocrinology
  • Physiology
  • Endocrinology, Diabetes and Metabolism
  • Cell Biology

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